Objective:To analyze the clinical characteristics of eosinophilic lung diseases(ELD) in children to enhance pediatricians′ understanding of ELD.Methods:In this retrospective cross-sectional study, a total of 149 children with ELD were recruited from Beijing Children′s Hospital, Capital Medical University between April 1, 2007 and March 31, 2022.Chi-square test, Fisher′s exact test, Mann-Whitney U test and Kruskal-Wallis test were used to analyze data and conclude clinical characteristics.Spearman correlation was used to analyze the correlation between eosinophils in peripheral blood and bronchoalveolar lavage fluid.Chi-square test and Kappa consistency test were used to compare the differences and consistency in diagnostic results between bronchoalveolar lavage fluid or lung biopsy and eosinophil elevation with chest imaging abnormalities. Results:(1)The isolated lung involvement was mostly caused by allergic bronchopulmonary aspergillosis(9 patients), and other system involvement by idiopathic hypereosinophilic syndrome(89 patients).(2)The main respiratory manifestations included coughing(90 cases, 60.4%) and expectoration(41 cases, 27.5%), while 23.5%(35 cases) of patients had no respiratory symptoms; 50.3% had digestive system involvement, and 40.9% had skin involvement.These were the two most commonly affected organs.(3)Spearman correlation was performed between eosinophils in peripheral blood and bronchoalveolar lavage fluid( r=0.3, P<0.05).Chi-square test was performed to compare ELD diagnosed by bronchoalveolar lavage fluid or lung biopsy with peripheral blood eosinophilia accompanied by abnormal chest imaging( P<0.05).Kappa consistency test(Kappa<0.2) showed poor consistency between the two diagnostic methods. Conclusions:ELD are present in children, and multiple etiologies may be pathogenic.Among children with ELD, the isolated lung involvement is mainly caused by allergic bronchopulmonary aspergillosis.The digestive system and skin are the most commonly affected organs, except for lungs.The correlation between eosinophil levels in peripheral blood and bronchoalveolar lavage fluid is poor.

Objective To investigate the effects of microgravity environment on hibernating myoblasts.Methods Hibernating myoblasts were cultured under real and simulated microgravity conditions for 10 days.RNA-seq analysis and immunofluorescence are used to analysis the impact of microgravity environment on cell growth and gene expression of myoblasts.Results Under the microgravity conditions,genes associated with proliferation were upregulated.Under simulated microgravity,there were more and higher proportion of Ki67 positive cells compared to normal gravity conditions.Conclusion The microgravity environment promotes the proliferation of hibernating myoblasts.

Poly(dimethyl siloxane)(PDMS)is suitable for the fabrication of space cell culture chips.It is necessary to perform highly stable hydrophilic modification to promote cell adhesion on PDMS surface.We modified PDMS surface by oxygen plasma treatment combining with physical adsorption in this article.PDMS,which was treated with oxygen plasma and sequentially coated with Poly-L-lysine or collagen(PLL-ox-PDMS,COL-ox-PDMS)with various solution concentration and kept in different environmental conditions,were characterized by contact angle and surface energy measurements,and atomic force microscopy(AFM).Cell growth conditions on bare PDMS and modified PDMS were compared,and the numbers of live cells cultured for 1-3 days were evaluated.Experimental results indicate that higher solution concentration and low storage temperature benefit the hydrophilicity stability.The contact angles of PLL-ox-PDMS stored in 4℃and COL-ox-PDMS were close to 60°and 65°on day 25 and 14,respectively.Both modified PDMS surfaces are suitable for cell adhesion and proliferation,and no cell layer falls offin 10 days.The modification method is especially suitable for applications such as medium and long term space cell culture.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective To explore the safer and more reasonable time of withdrawing nucleoside analogues antiviral therapy in women with chronic HBV infection during immune tolerance period. Methods The patients included in this study were 343 pregnant women with chronic HBV infection who received nucleoside antiviral therapy in Obstetrics and Gynecology Center of 302 Military Hospital of China. According to the time of withdrawing antiviral therapy after delivery, the patients were assigned to P0 group, i.e., withdrawal immediately after delivery, and the patients who stopped the drug 6 weeks after delivery were assigned to P6w group. The patients were compared between these two groups in terms of prevalence of ALT abnormality during pregnancy and postpartum, the peak value and occurrence time of postpartum ALT, and mother-to-child vertical transmission. Results The prevalence of postpartum ALT abnormality was 30.2％ in P0 group and 20.7％ in P6w group (χ2=4.129, P=0.046). Specifically, for the patients with abnormal liver function during pregnancy, the prevalence of postpartum ALT abnormality was 88.0％ and 39.4％ in the two groups respectively (χ2=14.043, P=0.001). While for the patients with normal liver function during pregnancy, the prevalence of postpartum ALT abnormality was 19.4％ and 16.6％ respectively (χ2=0.392, P=0.531). Mother-to-infant HBV transmission was blocked successfully in all the patients in spite of the time of withdrawing antiviral therapy. Conclusions For the pregnant women with chronic HBV infection who received oral nucleoside analogue antiviral agents to interrupt motherto-child transmission, the time of withdrawing antiviral agents did not show significant effect on the prevalence of postpartum liver function abnormality and rate of successful blocking mother-toinfant HBV transmission. However, for the patients with abnormal ALT during pregnancy, it is appropriate to continue the nucleoside analogue antiviral therapy after delivery.

This study was aimed to investigate the application rrles of Fu-Fang Ku-Shen (FFKS) injection in combination with modern medicines for the treatment of lymphoma in the real world,in order to provide references for rational clinical application of effective medication.Patients diagnosed as lymphoma and treated with FFKS injection from 22 triple-A hospitals in China were enrolled as research objects.Patients' treatment data were extracted from the hospital information system,which was established by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,in order to analyze the frequency distribution characteristics of modern medications combined in the treatment.Association rules and Apriori algorithm were used in the analysis of association characteristics of medication combination.The results showed that 3 674 cases fit the inclusion criteria were searched from the data warehouse.In the clinical practice,FFKS injection was frequently combined with moderu medications,such as antibiotics,glucocorticoids,5-HT receptor antagonists,immunomodulatory drags,proton pump inhibitor,chemotherapeutic drugs,and hepatic protector.Its associated modern medication combination showed special rrles,which was in consistency with the related diagnosis and treatment of lymphoma guideline.It was concluded that FFKS injection combined with modern medicine in the treatment of lymphoma in the real world was basically in consistency with related guidelines.It was focused on reducing the side effects of chemotherapy,prolonging survival time,and improving quality of life.It provided references for rational clinical drag application of lymphoma.

Objective: To observe the therapeutic response of radiosynovectomy with p-32 colloid on hemophilic arthropathy, and to assess the effects of radiosynovectomy with Denver Score on hemophilic arthritis staging. Methods: Radiosynovectomy with p-32 colloid was performed on 326 hemophilic arthritis patients (405 joints) , and recorded bleeding before and after treatment. The MRI performance of 102 joints was evaluated by using Denver scoring system, then was divided into 0-6 and 7-10 groups. Finally, the differences between 2 groups were analyzed. Results: Average pain score of all hemophilic arthritis patients at 6 months, 1, 2 and 3 years post treatment decreased from 3.2±2.4 (n=326) to 1.2±0.6 (n=285, P=0.021) , 1.7±0.5 (n=242, P=0.032) , 2.1±1.1 (n=212, P=0.030) and 2.2±1.6 (n=176, P=0.037) , respectively. The frequency of bleeding in 405 joints at 1, 2 and 3 years post treatment decreased from 15.1±3.6 to 2.1±0.7, 4.3±0.6, and 4.8±0.8 times per year (P<0.01) , respectively; Meanwhile, the proportions of significantly ameliorated joints’ activities were observed as of 68.50% (248/362) , 58.39% (181/310) , 55.67% (162/239) and 42.61% (75/176) , respectively. The frequencies of haemarthrosis at 1 and 2 years post treatment in patients with 0-6 Denver Score (45 target joints) reduced from 13.0±1.9 to 1.3±0.6 (P=0.002) and 3.1±0.9 (P=0.009) times per year, respectively, which also decreased in 7-10 group (57 target joints) from 16.6±2.1 to 3.1±0.9 (P=0.008) and 5.7±1.1 (P=0.004) times per year, respectively. There was no statistical difference between 0-6 and 7-10 groups before treatment in the terms of haemarthrosis frequency (P=0.773) . However, 7-10 group had higher haemarthrosis frequency at 1 and 2 years post treatment compare with 0-6 group (P=0.028 and 0.042, respectively) . Synovial volumes in 29 joints reduced after 6 month when compared with baseline [ (2 362.15±32.41) mm³ vs (3 012.40±39.78) mm³, t=7.621, P<0.001]. Conclusion Radiosynovectomy with p-32 colloid on haemophilic synovitis was a safe and effective procedure. The patients with Denver Score of 0-7 had lower frequency of haemarthrosis.

Objective: To analyze the clinical characteristics, diagnosis and treatment of bronchopulmonary foregut malformation(BPFM). Method: The clinical manifestations, imaging findings and treatment of 8 patients with BPFM were analyzed retrospectively from January 2006 to May 2016 in Beijing Children′s Hospital. Result: The age of children varied from 2 months to 7 years and 3 children were male while 5 female. Symptoms showed cough in 6 cases, fever in 4 cases, bucking when intaking of fluids or foods in 3 cases, tachypnea in 1 case, wheezing in 1 case, vomiting in 1 case, haematemesis in 1 case Pulmonary signs were decreased breath sounds in 4 cases, phlegm rale in 3 cases, shortness of breath in 2 cases, wheeze in 1 case, and retraction in 1 case. The upper gastrointestinal series showed abnormal fistulous tracts arising from the esophagus or the gastric fundus and extending into the mass in the lung. CT showed pulmonary sequestration and prompted the tube between lung and esophagus. Six children underwent pneumonectomy and esophageal fistula repair. They were discharged and their symptoms were improved. Two cases of children were discharged from a hospital without surgery. Conclusion Bronchopulmonary foregut malformation usually has its onset in early stage of life. The most common symptoms include recurrent pneumonia or bucking when intaking of fluids or foods. CT can demonstrate the bronchopulmonary sequestration and evaluate the communication with the gastrointestinal tract. The upper gastrointestinal series can demonstrate the abnormal tract directly. Pneumonectomy and esophageal fistula repair are the treatment of this disease.

Objective To investigate the correlation between serum cystatin-C (Cys-C) levels and cognitive impairment.Methods A perspective study involving 273 patients in our hospital was performed from 2013 to 2015.They were divided into the cognitive impairment group and the control group.Cys-C measurement results and cognitive impairment assessment scores were collected.Possible influence factors were adjusted,and the correlation between Cys-C levels and mild cognitive impairment was analyzed.Results The distribution of age,hypertension,diabetes mellitus,smoking,drinking,dyslipidemia,and creatinine showed significant differences between the groups at different Cys-C levels (all P＜0.05).There was a significant difference in the Cys-C level between the cognitive impairment group and the control group [(0.727±0.082) mg/L vs.(0.514±0.045)mg/L,t=23.68,P＜0.01].The Cys-C level was negatively correlated with the scores of mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA) in the cognitive impairment group (r =-0.318 and -0.572,P＜0.05).The incidence of cognitive impairment was elevated with increasing Cys-C levels (x2 =13.12,P＜0.01).Logistic regression analysis showed that high levels of Cys-C (OR=3.298,95％ CI:1.417-7.675,P=0.001),history of diabetes mellitus (OR=7.971,95％ CI:3.036-31.562,P =0.03),education level (OR =2.237,95 ％ CI:1.022-4.896,),smoking (OR =5.692,95 ％ CI:1.060-2.614),drinking (OR=1.227,95％ CI:0.083-1.228),and dyslipidemia (OR=2.267,95％ CI:1.177-4.366) are independent risk factors for cognitive impairment.Conclusions High serum cystatin C levels are closely correlated with the risk of cognitive impairment occurrence.