ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 （COVID-19）， and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system （FAERS） from January 1， 2015 to March 31， 2021. Information component （IC） and reporting odds ratio （ROR） methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis， and 45 positive drug adverse event signals were detected. Headache （IC₀₂₅=1.09， ROR₀₂₅=2.28）， pyrexia （IC₀₂₅=0.51， ROR₀₂₅=1.51） and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events with higher frequency. Autoimmune disorder （IC₀₂₅=4.42， ROR₀₂₅=24.03）， streptococcal infection （IC₀₂₅=4.12， ROR₀₂₅=19.82）， and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events. Acute lung injury， cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19， and some adverse events with high frequency and high death rate deserve further attention by medical staffs.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective:To report the clinical manifestations and total exon detection results of one case of MYSM1 gene complex heterozygosity mutation of bone marrow failure syndrome 4 and the results of total exon detection of her family to provide a case phenotype for the early diagnosis of bone marrow failure syndrome 4.Methods:A 1-month-old girl with severe anemia was sequenced with trio-WES. Similarly, the family was also sequenced with tribe-WES to confirm the molecular diagnosis. BWA, GATK, and other software were used for annotation analysis of sequencing results. After polymerase chain reaction, Sanger sequencing was performed by ABI3730 sequencer to verify the target sequence. Moreover, the verification results were obtained by the sequence analysis software. The clinical diagnosis of this girl was reported and the relevant pieces of literature were reviewed.Results:The girl presented with pancytopenia, polydactylism, nonspecific white matter changes, and cysts. However, CD3 -CD19 + B decreased. The child was identified with MYSM1 complex heterozygous mutation by whole-exome sequencing, NM_001085487.2:c.1607_c.1611delAAGAG and c.1432C>T, which was respectively inherited from his parents. Genealogy verification confirmed that the c.1432C>T mutation carried by the father was from the grandfather (father's father) , whereas the c.1607_c.1611delAAGAG mutation carried by the mother was from the grandfather (mother's father) , whereas the grandmothers, aunts, and uncle did not carry the mutation. The child was diagnosed with BMFS4 combined with clinical phenotypic and molecular genetic findings. Conclusion:This case provides a case phenotype for the early diagnosis of BMFS4 and extends the pathogenicity variation and phenotype spectrum of the MYSM1 gene. The newly discovered pathogenic variant of MYSM1 c. 1607_c.1611delAAGAG has not been reported at home or abroad.

Objective To study the incidence and risk factors of infection caused by methicillinresistant staphylococcus aureus (MRSA) with a targeted surveillance at intensive care unit (ICU) acquired MRSA infection in Tianjin area.Methods A prospective multi-center observational analysis of consecutive patients admitted to 15 adult ICUs from March 1,2012 through March 31,2014 was carried out.The ICUs were divided into four groups according to the type of the ICU.All of the patients were cared for with routine MRSA surveillance.A number of risk markers and prognostic factors were recorded.The risk factors contributing to ICU acquired MRSA were evaluated using a logistic regression model.Comparison of survival between groups was analyzed with Kaplan-Meier method.Results A total of 1 787 patients were enrolled,and 144 cases of them were MRSA infections.The patients with MRSA infection were significantly older than those with non-MRSA infection (P =0.043),length of ICU stay,length of antimicrobial therapy,the history of repeated administration of antibiotics in recent days,history of operation in the past five years,history of MRSA infection or colonization,frequent application of and the overall length of time for mechanical ventilation and central venous catheter and catheter-associated infection were significantly higher than those with non-MRSA infection.The survival rate of patients with non-MRSA infection were higher than those with MRSA infection (x2 =9.23,P =0.004).The rate of MRSA infection and MRSA colonization in 2013 were significantly lower than that in 2012,because the rate of hand hygiene rule execution and bacterial clearance rate were significantly higher in 2013.Multivariate Logistic regression analysis demonstrated that advanced age (OR =1.05,95％ CI:1.009-1.086),length of ICU stay (OR =1.05,95％ CI:1.01-1.08),history of MRSA infection or colonization (OR =1.33,95％ CI:1.82 -3.27),glucocorticoid therapy (OR =2.85,95％ CI:1.18-6.91),antacid medicine (OR =4.92,95％ CI:1.18-20.58),history of recent or repeated application of antibiotics (OR =3.26,95％ CI:1.06-4.59) catheter-associated infections (OR =2.22,95％ CI:1.08-4.59) were associated with ICU acquired MRSA infections.Conclusions Performing the rule of hand hygiene strictly as well as strengthening prevention and control of MRSA infections can effectively reduce the incidence of ICU acquired MRSA infections.The advanced age,length of ICU stay,history of MRSA infection or colonization,glucocorticoid therapy,antacids medicine,history of recent or repeated application of antibiotics,catheterassociated infections were independent risk factors of ICU acquired MRSA infections.

Objective To investigate the lung ultrasonography characteristics of community acquired pneumonia ( CAP) in children and to compare the value of lung ultrasonography in the diagnosis of CAP in children. Methods A total of 173 patients with CAP ( CAP group) were diagnosed by chest radiograph in our hospital,and 64 healthy children were treated with lung ultrasonography as the control group. The sono-graphic features of two groups were compared,and the positive rates of diagnosis of lung ultrasonography and chest radiograph in CAP group were also compared. Results It showed A-line disappearance ( 100%) , B-line presence ( 88. 4%) , pleural line abnormalities ( 98. 3%) , pulmonary consolidation ( 46. 2%) , bronchial sign(42. 8%),pleural effusion(9. 2%),lung sliding signs(97. 7%) in CAP group (P<0. 001). In the con-trol group,except the A-line disappearance,scattered in the B-line (34. 4%),the others were not present. The difference of the two groups was statistically significant (P<0. 001). A-line disappearance,B-line (or even fusion) ,pleural line abnormalities were the main signs of ultrasound in children with CAP, sensitivity and specificity were both 100%. The sensitivity of chest X radiograph was 100% and the specificity was 78. 0%. Conclusion The lung ultrasonic imaging features of CAP in children include A-line disappearance, with varying numbers and lengths of B-line, pleural line abnormalities, consolidation, bronchial signs, pleural effusion and so on. LUS can diagnose CAP accurately and reliably,with high sensitivity and specificity. It is simple and noninvasive, and has the advantage of being detected at any time and avoiding the damage of X-ray. So it is worth clinical application for children with respiratory tract diseases.

OBJECTIVE:To explore basic technology for synthesis of active ingredients of Ophiocordyceps xuefengensis,and provide necessary technical support for comprehensive development of O. xuefengensis sourse. METHODS:Submerged fermenta-tion method was used to cultivate the mycelium,achieving efficient synthesis of active ingredients by controlling medium composi-tion and cultivation conditions. Using the bacteria as starting strain,the effects of different carbon sources (sucrose,glucose and soluble starch),different nitrogen sources (peptone,yeast extract powder,yeast extract,sodium nitrate,potassium nitrate and urea),different vitamin B(vitamin B1 and vitamin B complex)and different initial pH(pH was set at 4,5,6,7,8 and 9,re-spectively)on mycelial growth,extracellular and intracellular polysaccharide synthesis,cordycepin synthesis and intracellular triter-penoid synthesis were investigated to screen the optimal medium composition. RESULTS:The optimal carbon source,nitrogen source,vitamin B and initial pH were sucrose,yeast extract powder,vitamin B1 and 8,respectively. High biomass and metabolite accumulation levels can be obtained when carbon source was sucrose,nitrogen source was yeast extract powder,adding 0.1 g/L vi-tamin B1 with initial pH of 8. CONCLUSIONS:O. xuefengensis can efficiently accumulate metabolites,and achieve the optimiza-tion of strain cell growth and synthesis of active metabolite by optimizing and controlling the fermentation process.

Objective To investigate the effectiveness and safety of anterior vitrectomy combined with capsular retractor and Cionni modified capsular tension ring (MCTR) in traumatic lens subluxation surgery with anterior vitreous prolapse.Methods This study comprised 16 patients (16 eyes) of traumatic lens subluxation with anterior vitreous prolapse,in which iridodialysis was in 3 eyes,express implantation in 1 eye and Ahmed glaucoma valve implantation in 1 eye.According to the severity of lens subluxation,the patients were divided into three levels,including 90°-120° (7 eyes),120°-180° (5 eyes) and 180°-270° (4 eyes).Considering the anterior vitreous prolapse,anterior vitrectomy or/and pars plan vitrectomy was conducted with assistance of triamcinolone acetonide.After continuous curvilinear capsulorhexis,two to four capsular retractors were placed in the capsulorhexis to support and center the capsule.MCTR was inserted with scleral suture fixation after phacoemulsification.At last,the foldable IOL was implanted to capsular bag.Postoperative visual acuity,intra-and post-operative complications,anterior capsular opening,IOL positions and intraocular pressure (IOP) were assessed during 3 months' follow up.Results All patients had successfully undergone phacoemulsification,MCTR insertion and IOL implantation.Seven eyes were inserted with 2-eyelet MCTR and nine eyes were inserted with 1-eyelet MCTR.The postoperative visual acuity was better than 0.5 in 9 eyes,between 0.3 and 0.5 in 4 eyes,between 0.1 and 0.3 in 2 eyes,and less than 0.1 in 1 eye.Compared with pre-operation,the difference in the visual acuity was statistically significant (x2 =17.503,P =0.000).The scheimpflug images obtained from the Pentacam,which demonstrated that the IOL was well centered,and no MCTR and IOL decentration occurred.The common intraand post-operative complications were residual cortex,aqueous misdirection syndrome,anterior capsular tears,anterior capsular phimosis and posterior capsular opacification.Conclusion The effective application of anterior vitrectomy is the key point to reduce surgical complications.Anterior vitrectomy combined with insertion of capsular retractor and MCTR is an ideal surgical option for patients of traumatic lens subluxation with anterior vitreous prolapse.

Objective To evaluate regulatory effects of miRNA-146a on peripheral blood CD4 + T lymphocytes from patients with psoriasis vulgaris, and to investigate the role of miRNA-146a in the pathogenesis of psoriasis vulgaris. Methods Totally, 30 patients with psoriasis vulgaris and 30 healthy human controls were enrolled into this study. Venous blood samples were obtained from these subjects, and CD4 + T lymphocytes were isolated from these samples by using magnetic activated cell sorting (MACS). Real-time quantitative PCR (RT-PCR)was performed to measure the expression of miRNA-146a in peripheral blood CD4+ T lymphocytes, and enzyme-linked immunosorbent assay(ELISA)to determine plasma levels of interferon-γ(IFN-γ)and interleukin 4(IL-4). Some CD4+ T lymphocytes were divided into 3 groups to be transfected with 50 nmol/L negative control miRNA (control group), miRNA-146a mimics(miRNA-146a group)or miRNA-146a inhibitor (miRNA-146a inhibitor group). After 24-hour additional culture, flow cytometry was conducted to determine the number of Th1 and Th2 cells, Western-blot analysis and RT-PCR were performed to measure the protein and mRNA expressions of IFN-γ receptor α (IFN-γRα), T-box expressed in T cells (T-bet)and GATA-binding protein-3 (GATA-3)respectively, and ELISA was carried out to determine the levels of IFN-γ and IL-4 in supernatants of CD4 + T lymphocytes. Results Compared with the healthy control group, the patient group showed significantly increased miRNA-146a expression in peripheral blood CD4 + T lymphocytes (243.81% ± 94.32% vs. 105.74% ± 22.93%, t = 6.653, P < 0.01)and plasma IFN-γ level (27.69 ± 7.64 ng/L vs. 9.75 ± 2.81 ng/L, t = 4.237, P <0.01). Moreover, miRNA-146a expression was positively correlated with plasma IFN-γ level in the patients(r = 0.837, P <0.01). After 24-hour culture in vitro, there was a significant increase in the number of Th1 cells, protein and mRNA expressions of T-bet, and supernatant level of IFN-γ, but a significant decrease in the protein expression of IFN-γRα in the miRNA-146a group compared with the control group (all P < 0.01). However, no significant differences were observed in the number of Th2 cells, mRNA or protein expressions of GATA-3, or supernatant level of IL-4 among the control group,miRNA-146a group and miRNA-146a inhibitor group (all P > 0.05). Conclusion miRNA-146a may play an important role in the pathogenesis of psoriasis vulgaris by participating in the regulation of peripheral blood CD4+ T lymphocytes via affecting Th1 cell differentiation and function.

Objective To investigate the value of electronic bronchoscopy in the diagnosis of children respiratory diseases. Methods The electronic bronchoscopy results in 400 children with respiratory disease were retrospectively analyzed. Results In 400 children, there were 246 cases with simple endobronchial inflammation, 67 cases with bronchial malacia, 38 cases with bronchial stenosis, 23 cases with bronchial foreign , 4 cases with tracheal bronchus, 4 cases with epiglottic cyst, 3 cases with bronchiectasis, 3 cases with endobronchial granulation, 3 cases with laryngomalacia, 2 cases with vascular ring compression of the trachea, 2 cases with laryngeal web, 1 case with subglottic cyst, 1 case with subglottic neoplasm, 1 case with tracheoesophageal fistula, 1 case with bronchial atresia (left) and 1 case with trachea cyst. All the children had no serious complications. Conclusions Electronic bronchoscopy can effectively improve the level of diagnosis and treatment of children' s respiratory system disease, and it is worth of clinical promotion.

Objective To compare the effect of nursing students acting as social volunteers to participate in gerontological nursing practice teaching with traditional practice teaching mode, and promote the reform of teaching mode in nursing practice. Methods Students of two classes from department of nursing, medical college of Wuhan University of Science and Technology were selected as research objects. In class one nursing students acted as social volunteers to participate in gerontological nursing practice teaching (the experimental group), In class two nursing students took practice in geriatric wards according to traditional practice mode(the control group). The practice effect was compared between two groups. Results The average final grade of the experimental group was 86.50, and 78.51 in the control group. Ridit analysis revealed that, setting class one as the experimental group, R=0.796 8,95% confidence interval was 0.715 1-0.878 4, in the control group, R =0.500 0. The investigation showed that the experimental group and the control group were different in moral elevation aspect, teaching level, capability improving aspect and employment promotion aspect, the difference was significant (P<0.01). Conclusions The mode of nursing students acting as social volunteers to participate in gerontological nursing practice teaching has advantage over traditional practice teaching, and it can gain satisfying teaching effect.