Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

CRISPR/Cas9 technology has driven the development of various fields in life science.With continuous deepening of its understanding,researchers have made multiple improvements and optimizations to adapt to various application scenarios.The optimization of CRISPR/Cas9 technology has also provided breakthroughs in the establishment of genetically modified mouse models.This article briefly reviews the development process of CRISPR/Cas9 technology and summarizes optimization strategies of CRISPR/Cas9,establishment of conditional knockout/knockin gene-modified mouse models,and delivery systems for CRISPR/Cas9 elements and HDR templates.

Objective:To investigate the effect of radon on the expressions of miR-16, miR-106b, miR-449a, let-7g, miR-21, miR-221 and miR-34a in peripheral blood plasma of miners.Methods:A total of 46 randomly selected miners worked underground(the underground group)and 38 miners worked aboveground (the control group). MiRNA levels in the underground and control groups were detected by qRT-PCR and their relationship with cumulative effective dose was further analyzed.Results:The levels of miR-106b, miR-21, miR-221 in plasma of the study group were significantly higher than those in the control group( Z=-2.32, -2.47, -2.79, P<0.05), the corresponding Fc values were 1.61, 1.75, 1.30, respectively. The levels of miR-16, miR-449a, let-7g and miR-34a were slightly higher than those in the control group ( P>0.05). After controlling of confounding factors such as age, BMI and smoking, the alteration of miR-16, miR-106b, let-7g, miR-21 and miR-221 in plasma of the underground group were positively correlated with the cumulative effective dose( t=2.50, 3.31, 2.60, 2.95, 3.25, P<0.05). No significant difference was observed in the plasma levels of miR-449a and miR-34a between the two groups ( P>0.05). Conclusions:miR-106b, miR-21 and miR-221 could be used as potential biomarkers of radon exposure.

Objective To investigate and analysis the epidemiological characteristics of a cluster epidemic of COIVD-19 in a collective workplace in Tianjin, evduate the prevention and control measures based on limited evidence and experience in early period of COVID-19 epidemic. Methods Descriptive research method was used to describe the distribution and other epidemiological characteristics of the cluster cases of COVID-19. Results Since the onset of the first index case on January 15, ten confirmed COVID-19 cases had occurred in the workplace, and the epidemic had spread from the workplace to 4 families, infecting 7 family members. The median age of 17 cases was 55 (19-79) years. All the 10 employee cases were males, and in 7 family cases, 3 were males and 4 were females. Of the employee cases, 8 worked in CW workshop and 2 worked in administrative office building. The median exposure-onset interval of all the cases was 4 (0-12) days, and the median exposure-onset interval was 4.5 days in the employee cases and 4 days in the family cases. The median onset-medical care seeking interval was 4 days in the non-isolated cases, 2.5 days in the cases with home isolation after onset, and 0.5 day in the cases with home isolation before onset. Conclusion The clustering of COVID-19 cases was observed in this workplace in Tianjin, which affected 4 families. In the early stage of the epidemic, accurate and rapid blocking and control measures can completely prevent the large-scale spread of COVID-19.

Objective To observe potential effect of radon hot springs on the changes of cell cycle and its regulatory proteins of CDK1,CDK2,CDK4,CDK6,CyclinD1,CyclinE1,WEE1,CDC25A in the peripheral blood lymphocytes of residents.Methods A random sampling method was used to persons 46 persons from the residents around radon hot spring in Wentang town,and 39 persons were selected from the control area without radon exposure.Flow cytometry was used to detect the changes of cell cycle and the expressions of cell cycle-related regulatory proteins.Multiple linear regression method was used to analyze the relationship between the expressions of cell cycle regulatory proteins and radon exposure.Results The percentages of cells at G0/G1 phase and S phase in lymphocytes were different in the two groups (t =2.250,-2.382,P ＜ 0.05).The expression levels of CDK1,CDK6 and CyclinE1 in the peripheral blood lymphocytes of radon hot spring group were significantly decreased (t =4.770,11.419,5.238,P ＜ 0.05) and negatively correlated with radon exposure (t =-5.097,-11.128,-5.117,P ＜0.05).The expression levels of CDK2,CDK4,CyclinD1,WEE1 and CDC25A in the peripheral blood lymphocytes of radon hot spring group were increased but not significantly(P ＞ 0.05).Conclusions The incidences of a higher ratio of S-phase cells and lower expression levels of CDK1,CDK6 and CyclinE1 in the peripheral blood lymphocytes of residents in Wentang town may be related to long-term radon exposure.

Objective To analyze the biological dose estimation ability of the radiation health technology institutions nationwide from 2015 to 2017,and their development in recent years.Methods SPSS 19.0 software was used to analyze and pack the data involved in the 2015-2017 year assessments by using x2 test.Statistical analysis was conducted of qualification rate,excellent rate,participating units and dose estimation deviation distribution.Results The qualification rate gradually increased from 2015 to 2017.Compared with 2015,the passing rate significantly increased in 2017 with statistically significant difference(x2 =3.978,P ＜0.05).A total of 53 units participated in the biological dose assessment,of which 30 units were involved over the three consecutive years,accounting for 57％.In the distribution of the relative deviation of dose estimates made by the units participating in the three-year assessment,the proportion of estimated deviations in the range of 5％-10％ increased whereas those in the range of 15％-20％ and ＞ 20％ decreased.Conclusions During 2015-2017 year period the biological dose estimation ability of all units involved in the assessment nationwide was basically stable,with gradually improved test level,qualification rate and steady excellence rate.

Objective To explore the role of γ-synuclein(SNCG) siRNA in the radiosensitivity of breast cancer T47D cells.Methods SNCG siRNA was synthesized according to the coding sequence of SNCG mRNA and then transiently transferred into T 47D cell with lipofectamine .The expression of SNCG gene and protein was detected by RT-PCR and Western-blot, respectively.Cells were divided into three groups, SNCG siRNA interference group , negative control group and blank control group , which were irradiated with different doses of 60 Coγ-rays.Cell radiosensitivity was evaluated by colony formation assay , cell proliferation was assayed by CCK-8 kit, and the protein expressions of phosphorylated-AKT and mTOR were detected by Western blot assay .Results Compared with blank control cells , the expressions of SNCG gene and protein in the SNCG siRNA transferred T 47D cells were efficiently diminished .Cell colony formation results showed that , under 4, 6, 8 Gy irradiation, the cell survival of siRNA transfection group was lower than that of control group (t=5.449, 8.882, 21.503, P<0.05).CCK-8 experiments showed that the cell proliferation abilities of siRNA group at 24, 48, 72 h after 6 Gy irradiation were lower than those of control group (t=5.603, 4.839, 6.115, P<0.05).In addition, after 6 Gy irraddaition, the AKT and mTOR phosphorylation levels in the siRNA group were more obviously reduced compared with blank groups , but the total AKT and mTOR had no changes .Conclusions Transfection of SNCG siRNA can enhance the radiosensitivity of breast cancer cells probably by inhibiting p -AKT signal pathway .

Objective To explore the effects of high background radiation on the expressions of miR-16, miR-106b, miR-449a, miR-34a and let-7g in peripheral blood plasma of the residents .Methods Totally 110 healthy female long-term local residents aged over 50 years were randomly selected from the high background radiation area and the control area , while their age, body mass index(BMI) and other indicators were surveyed .The relative expression levels of miRNAs in peripheral blood plasma of these women were quantitatively detected by real-time fluorescence quantitative PCR ( RT-PCR) .Then t-test was used to analyze the cumulative dose , age and BMI between the high background and control group .Mann-Whitney U-test was used for statistical analysis of miRNA expression levels between two groups , and the multiple regression analysis was used finally .Results Compared with the control group , the cumulative dose of individuals in the high background group was about four times higher (t=42.803, P<0.05), and the levels of miR-16 and miR-106b in plasma of high background group were down-regulated, while the level of miR-449a was up-regulated ( Z =4.180, 2.422, 2.794, P <0.05 ).After controlling of confounding factors such as age and BMI , the expression levels of miR-16 and miR-106b were negatively correlated with the cumulative dose of individuals (P<0.05).On the contrary, no significant correlation was observed between the levels of miR-449a, miR-34a, let-7g and the individual cumulative dose (P>0.05).Conclusions miR-16 and miR-106b may serve as biomarkers for the early stage of low dose radiation health effects .

Objective To investigate the expressions of miR-210-3p,miR-221-3p,miR-21-5p and miR-150-Sp in the plasma of breast cancer patients before and after radiotherapy in order to establish reliable early biomarkers of non-uniform radiation injuries.Methods Blood samples were collected from 13 patients before radiotherapy (0 Gy) and 24 h after radiotherapy of 2,10,20,30 Gy.The miRNAs in the blood plasma were detected with qRT-PCR.Results The levels of miR-210-3p,miR-221-3p,miR-21-5p had no significant difference among different dosage groups after radiotherapy(P ＞ 0.05).There was no significant difference between the expression of miR-150-5p before and after 2 Gy radiotherapy (P ＞ 0.05).While the relative level of miR-150-5p gradually decreased to 0.808,0.605,0.565 (x2 =18.76,P ＜ 0.05) with increased accumulative dosage of 10,20,and 30 Gy,respectively.In addition,the miR-150-5p expression levels had no relationship (P ＞ 0.05) with situations (positive or negative group) of human epidermal growth factor receptor 2 (HER2),estrogen receptor (ER) and progesterone receptor (PR) in the breast cancer cells.Conclusions Ionizing radiation could reduce the expression of miR-150 in the plasma of breast cancer patients in a dose-dependent manner.

Objective To investigate diagnostic magnetic resonance imaging features of orbital Langerhans cell histocytosis (LCH)and improve its diagnostic accuracy.Methods The symptoms and image data of fourteen histophathology verified orbital LCH cases are reviewed and analyzed.Results Nine patients had swollen eyelids,accompanying with symptoms of inflammation, esphthalmos and orbital masses.One case had cough symptom and another had diabetes insipidus.Of these fourteen cases,seven occurred in right orbital,six occurred in left orbital and one involved bilateral orbital.As to the location of LCH,six cases located in super-lateral wall of the orbit,five cases located in lateral wall of the orbital,and three cases located in roof of orbital.On MRI, thirteen cases lesions show hypo or iso signal intensity on T1 WI,and eleven cases lesions show heterogeneous hyper or iso signal in-tensity on T2 WI.The lesions of eosinophilic granuloma has clear border,which differentiate it from other types.After contrast en-hancement,MR imaging showed marked inhomogeneous enhancement.Conclusion MRI is the primary modality in diagnosing of or-bital LCH,clearly and accurately manifesting the extent of orbital LCH.It will be helpful to diagnose LCH timely if combining with clinical data.MR could provide reliable information for making surgical operation and treatment plan.