BACKGROUND: The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9. METHODS: H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models. RESULTS: The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically. CONCLUSION The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Animals ; Antibodies, Monoclonal/therapeutic use* ; Antibodies, Neutralizing/therapeutic use* ; Antibodies, Viral ; Hemagglutinins ; Humans ; Influenza A Virus, H1N1 Subtype ; Influenza A Virus, H3N2 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines ; Influenza in Birds ; Influenza, Human/prevention & control* ; Mice

Objective: To understand the proper handwashing behavior of preschool children and primary school students in Beijing, and to analyze associated family factors to provide reference for further health intervention related to handwashing. Methods: From November to December 2020, parents of 36 kindergartens and 18 primary schools in 9 districts of Beijing were investigated online by using a self designed questionnaire with questionnaire star software. The contents of the survey included the basic situation of children and their families, parents correct knowledge of the prevention of novel coronavirus pneumonia, their perception of the epidemic risk, the provision of handwashing guidance for children, and children s handwashing behavior. Results: The proportion of proper handwashing of preschool children was 70.2%, which was higher than that of primary school students (61.9%) ( χ 2=57.63, P <0.01). The proportion of parents of preschool children who correctly knew handwashing related knowledge (36.2%, 33.4%), had low perception of epidemic risk (28.9%, 25.4%), and provided handwashing guidance (99.1%, 97.9%) was higher than that of parents of primary school students, and the differences were statistically significant ( χ 2=6.72, 22.84, 18.68, P <0.05). But the proportion of parents of preschool children who had high self efficacy (75.7%, 78.2%)was lower compared to parents of primary school students( χ 2=6.43, P =0.04). Multivariate regression results showed that whether preschool children or primary school students, urban areas and parents had high self efficacy, low risk perception, and provided hand washing guidance for children, children were more likely to wash their hands correctly. For preschool children, non only children were 0.79(95% CI =0.69-0.92) times more likely to wash their hands correctly than only children. For primary school students, girls were 1.21(95% CI =1.06- 1.39 ) times more likely to wash their hands correctly than boys, and parents who know knowledge correctly were 1.20(95% CI = 1.04 -1.40) times more likely to know it incorrectly( P <0.05). Conclusion Proper hand washing behavior of preschool children is higher than that of primary school students. Parental awareness of COVID-19 epidemic, handwashing behavior, self efficacy and guidance behavior have effects on the development of children s health behavior. Measures should be taken to enhance parents awareness of infectious diseases and their ability and self efficacy of guiding children in disease prevention.

Objective:To investigate the phenotype, genotype and clinical course of centronuclear myopathy(CNM) in children.Methods:Clinical data of patients with CNM in the Department of Pediatrics, Peking University First Hospital from October 2008 to December 2018 were collected.The clinical, pathological and genetic data of 9 children with CNM were retrospectively analyzed.The patients were followed up from 8 months to 8.6 years [(4.4±3.1) years].Results:(1)Clinical phenotype: there were 6 males and 3 females with onset age ranging from 1 d to 10 years.Generalized muscle weakness or motor retardation was the main complaint in 8 cases, while elevated muscle enzymes presented in 1 case.Varying degrees of skeletal muscle weakness were noted on examination in all patients, with facial muscle involvement in 4 cases.Six patients were followed up.No deterioration in motor function was noted, while 2 patients had improvement.There was no significant cardiac involvement in all 6 patients.Scoliosis occurred in 4 patients.Restrictive ventilator disorder developed in 2 out of the 5 patients who underwent pulmonary function tests.(2)Genotype: 8 out of 9 patients underwent gene test, confirmed gene diagnosis in 4 patients including: DNM2 gene (c.1856C>T, c.1893+ 1G>A was novel) de novo heterozygous mutation in 2 cases, RYR1 gene (c.2044C>G, c.6823G>A, both were novel) compound heterozygous mutation in 1 case, and TTN gene (c.107377+ 1G>A, c.2106_2107 insAAGCTGTA was novel) compound heterozygous mutation in 1 case. Conclusions:The course of centronuclear myopathy is relatively static, with more frequent involvement of facial muscles than myocardium.This study enriched the gene mutation spectrum of centronuclear myopathy (4 novel mutations).

Objective:To investigate the effects of different adding time of human milk fortifier on the incidence of complication and catch-up growth of low birth weight premature infants.Methods:A total of 150 low birth weight premature infants were assigned to early fortification group, middle fortification group and delayed fortification group, each 50 cases. In early fortification group, adding human milk firtifier in the enteral intake of 70-85 ml/kg·d, 70-85 ml/kg·d and 86-100 ml/kg·d in the middle fortification group and delayed fortification group, respectively. The incidence of complication and growth development during hospitalization were compared between three groups. Meanwhile, the catch-up growth of low birth weight premature infants were follow-up in three groups.Results:The weight growth rate in the early fortification group was (15.45±2.54) g kg -1·d -1, and middle fortification group was (15.13±2.21) g kg -1·d -1, and the delayed fortification group was (13.50±2.02) g kg -1·d -1, the difference was statistically significant ( F value was 10.676, P<0.01). The incidence of feeding intolerance in the early fortification group was 20.0% (10/50), he middle fortification group was 6.0% (3/50), and delayed fortification group was 4.0% (2/50), the difference was statistically significant ( χ2 value was 8.444, P<0.05). However, there was no significant difference in the incidence of complication and growth development during hospitalization between the three groups ( P>0.05). Repeated measures ANOVA showed that, the differences of body weight, body length and head circumference were statistically significant for the time main effect and group main effect ( F values were 6.291-965.062, P<0.01). In addition, the differences of body length were statistically significant for the group by time interaction ( F value was 5.752, P<0.01). The body weight in the corrected postnatal age 2 months in the early fortification group, middle fortification group and delayed fortification group were (3 017.83±347.40), (2 897.27±315.35), (2 761.22±319.23)g, and the body weight in the corrected postnatal age 3 months were (3 947.67±461.99), (3 844.85±434.68), (3 647.78±418.62)g; the body length in the corrected postnatal age 3 months of the early fortification group, middle fortification group, and the delayed fortification group were (57.87±3.97), (57.19±2.98), (54.27±2.94) cm) and head circumference were (38.13±3.75), (37.13±4.28), (35.42±2.82)cm, the difference was statistically significant ( F values were 6.987, 5.479, 15.035, 6.473, P<0.01). Conclusion:Human milk firtifier with enteral intake of 70-85 ml/kg·d contributes to catch-up growth in low birth weight premature infants, as well as not to the increases in the incidence of feeding intolerance.

Current studies have confirmed that liver diseases are closely related to intestinal microorganisms; however, those studies have mainly concentrated on bacteria. Although the proportion of intestinal microorganisms accounted for by colonizing fungi is very small, these fungi do have a significant effect on the homeostasis of the intestinal microecosystem. In this paper, the characteristics of intestinal fungi in patients with chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease and cirrhosis are summarized, and the effects of intestinal fungi and their metabolites are analyzed and discussed. It is important to realize that not only bacteria but also intestinal fungi play important roles in liver diseases.

Objective: To construct a method to express ScFv antibody from PCR products, and use it in phage display for high-throughput ScFv expression. Methods: Cytomegalovirus (CMV) promotor, ScFv and BGH-Poly A gene fragments were amplified by PCR. Overlapping PCR was used to form a tandemly linear cassette gene. By transiently transfected into 293T cells, ScFv antibodies expression of cassette gene were tested by Western blot, enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent antibody (IFA). Ninety-six clones of antibody genes in phage library were selected and expressed by cassette expression system. The expression level was evaluated and analyzed. Results: Three fragments were obtained and a cassette expression system formed. Cassette expression system worked successfully in 293T cells, as a Mr.38×10³ brand could observed in Western blot assay. The expressed antibody could specifically bind to its antigen by result of ELISA and IFA. This cassette expression system could also be used in phage display for high-throughput panning. Conclusions The cassette expression system was constructed successfully and high-throughput antibody expression has been achieved.

Platinum antitumor drugs are widely used for clinical treatment because of their unique antitumor mechanisms, significant antitumor effects, and broad antitumor spectrum. Yet shortcomings such as toxic side effects, drug resistance and cross-resistance of platinum-based drugs have limited their further application. Platinum-intercalator conjugates possess different antitumor mechanisms from those of classic platinum drugs, and have unique advantages in overcoming the disadvantages of classic platinum antitumor drugs. The platinum-intercalator conjugates can be classified into six categories based on the different DNA-intercalator: platinum-acridine, platinum-quinoline, platinum-indole, platinum-naphthalimides, platinum-anthraquinone and platinum-based antitumor agents containing other types of intercalating groups. This article summarizes the research progress of platinum-based antitumor drugs containing DNA insertion groups in recent years.

Objective To investigate the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in Chinese patients with ischemic stroke . Methods In this multi‐center study ,2 310 continuously inpatients with ischemic stroke diagnosed in 20 stroke screening and prevention project base hospitals from June 2015 to M ay 2016 were enrolled . Carotid ultrasonography and transcranial color‐coded sonography or transcranial Doppler were performed in all patients to confirm the presence of cerebral artery stenosis or occlusion . According to the distribution of lesions ,the subjects were divided into 2 groups :the simple intracranial artery stenosis group and the simple extracranial artery stenosis group . T he difference of risk factors between the two groups was compared . Results Of the 2 310 patients with ischemic stroke ,1 516 ( 65 .6% ) had simple intracranial artery stenosis and 794 ( 34 .4% ) had simple extracranial artery stenosis . T he incidence of anterior circulation artery stenosis was higher in the group of intracranial artery stenosis than that in the extracranial artery stenosis group ( 68 .1% vs 48 .7% , P ＜0 .001) . Posterior circulation artery stenosis and combined anterior with posterior circulation artery stenosis were more common in patients with extracranial artery stenosis group than those in intracranial artery stenosis group ( 36 .4% vs 22 .1% ,14 .9% vs 9 .8% ;all P ＜0 .001) . Univariate analysis of risk factors for stroke showed that patients with intracranial arterial stenosis had a higher prevelence of hypertension , diabetes ,obesity ,and family history of stroke ,and their systolic blood pressure ,diastolic blood pressure , body mass index ( BM I) ,fasting blood‐glucose ,glycosylated hemoglobin ,triacylglycerol ,total cholesterol , and low‐density lipoprotein cholesterol were significantly higher than those in the extracranial arterial stenosis group ( all P ＜ 0 .05 ) . T he proportion of elderly ( ≥ 65 years old ) ,male and smokers in the extracranial arterial stenosis group was significantly higher than that in the intracranial arterial stenosis group ( all P ＜0 .05) . Multivariate logistic regression analysis showed that elderly ( ≥65 years old) ,male , and smoking history were independent risk factors for extracranial arterial stenosis ( OR＝ 2 .012 ,1 .637 , 1 .325 ,respectively ;all P ＜0 .05) . While hypertension ,diabetes ,less physical activity ,and high BM I levels were independent risk factors for simple intracranial arterial disease ( OR ＝ 1 .301 ,1 .252 ,1 .248 ,1 .030 , respectively ;all P ＜0 .05) . Conclusions There are significant differences in the distribution characteristics and risk factors of intracranial and extracranial aterial lesions in patients with ischemic stroke in China .

Objective To optimize the extraction process of mixed volatile oil from Forsythiae Fructus, Saposhnikoviae Radix and Magnoliae Flos and inclusion process of β-cyclodextrin (β-CD). Methods With yield ratio of volatile oil as evaluation index, single factor experiments were used to study the extraction process of volatile oil;saturated aqueous solution was used, with inclusion rate of volatile oil as index, and orthogonal design was adopted to examine effects of charge ratio of volatile oil and β-CD, inclusion temperature and inclusion time on the inclusion process; X-ray scattering technique, infrared spectroscopy and scanning electron microscopy were used to characterize the inclusion compound. Results The optimum extraction process of volatile oil was soaking fine powder extracted 5 hours with 10 folds the amount of water. The optimum conditions of inclusion process were as follows:mixed ratio of volatile oil (mL) and β-CD (g) was 1:10; inclusion temperature was 50 ℃; the inclusion time was 2 h. X-ray scattering technique, infrared spectroscopy and scanning electron microscopy proved the inclusion compound had been formed. Conclusion Optimum extraction and inclusion processes are stable and feasible, and can provide research foundation for further research and development of preparation.

Objective To analyze the correlation between smoking and occurrence of intracranial artery stenosis.Methods From June 2015 to May 2016,a total of 10 711 inpatients with transient ischemic attack (TIA) or ischemic stroke from 20 basel hospitals of nationwide were enrolled using a cross-sectional study,76 patients with unknown smoking and smoking cessation years were excluded.Finally,a total of 10 635 patients were enrolled.Transcranial color coded sonography and/or transcranial Doppler were used evaluate the intracranial artery stenosis lesions.The basic risk factors for cerebrovascular disease (age,sex,smoking and smoking years,whether smoking cessation and years,hypertension,diabetes,hyperlipidemia,atrial fibrillation,and family history of stroke) were recorded.According to the different smoking years,the smoking years were divided into five groups:non-smoking,smoking time ≤10-year,11 to 20-year,21 to 30-year,and >30-year groups for trend chi square test.According to the different smoking cessation years in the smokers,the smoking cessation years were divided into four groups:non-cessation,cessation time 1 to 10-year,11 to 20-year,and >20-year groups for trend chi square test.The effects of different smoking years and different smoking cessation years on the occurrence of intracranial arterial stenosis were analyzed.Results The incidence of intracranial artery stenosis in the smokers (40.4%[1 433/3 547]) was significantly higher than that in the non-smoking patients (29.4%[2 085/7 088]).There was significant difference (χ2=128.850,P<0.01),and the incidence of cerebral infarction in the smokers (91.6%[3 250/3 547]) was significantly higher than the non-smokers (85.0%[6 027/7 088]).There was significant difference (χ2=92.328,P<0.01).Smoking was an independent risk factor for intracranial artery stenosis (OR,1.603;95%CI 1.456-1.765;P<0.01).With the increase of smoking years,the detection rate of intracranial arterial stenosis increased gradually (trend χ2=115.437,P<0.01).Whether giving up smoking had no significant effect on the incidence of intracranial artery stenosis in patients with ≥20 years of smoking (trend χ2=1.043,P=0.307).Conclusions Smoking is an independent risk factor for affecting intracranial artery stenosis;the risk of disease increases with the number of smoking years.Long-term smokers (≥20 years) cannot reduce the effect on intracranial artery stenosis,even if they give up smoking.