Adverse events in the treatment of spinal muscular atrophy in children and adolescents with nusinersen: A systematic review and meta-analysis.

Objectives: To systematically analyze adverse events (AEs) in treatment of spinal muscular atrophy (SMA) with Nusinersen in children and adolescents. Methods: The study is registered on PROSPERO (CRD42022345589). Databases were searched and literature relating to Nusinersen in the treatment of spinal muscular atrophy in children from the start of database establishment to December 1, 2022, was retrospectively analyzed. R.3.6.3 statistical software was used, and random effects meta-analysis was performed to calculate weighted mean prevalence and 95% confidence intervals (CI). Results: In total, 15 eligible studies were included, with a total of 967 children. Rate of definite Nusinersen-related AEs was 0.57% (95% CI: 0%-3.97%), and probable Nusinersen-related AEs 7.76% (95% CI: 1.85%-17.22%). Overall rate of AEs was 83.51% (95% CI: 73.55%-93.46%), and serious AEs 33.04% (95% CI: 18.15%-49.91%). For main specific AEs, fever was most common, 40.07% (95% CI: 25.14%-56.02%), followed by upper respiratory tract infection 39.94% (95% CI: 29.43%-50.94%), and pneumonia 26.62% (95% CI: 17.99%-36.25%).The difference in overall AE rates between the two groups (Nusinersen group and placebo group) was significant (OR = 0.27,95% CI: 0.08-0.95, P = 0.042). Moreover, incidence of serious adverse events, and fatal adverse events were both significantly lower than in the placebo group (OR = 0.47, 95%CI: 0.32-0.69, P < 0.01), and (OR = 0.37, 95%CI: 0.23-0.59, P < 0.01), respectively. Conclusion: Nusinersen direct adverse events are rare, and it can effectively reduces common, serious, and fatal adverse events in children and adolescents with spinal muscular atrophy.

The Effect of Cyclosporin A on Aspergillus niger and the Possible Mechanisms Involved.

Aspergillus niger is one of the major pathogenic fungi causing postharvest grape decay. The development of antifungal agents is beneficial to reduce the loss of grapes during storage. The aim of this study was to investigate the antifungal mechanism of cyclosporin A (CsA). It was indicated that the rot development on grapes caused by A. niger was almost completely inhibited with CsA in vivo at a concentration of 200 mg/L. The transcriptomic analysis revealed that the expression levels of genes involved in rRNA processing and ribosome biogenesis were down-regulated, whereas those related to ß-glucosidases and chitinases were up-regulated. The results implied that CsA may disturb rRNA and ribosome formation to obstruct protein synthesis, accelerate chitin and glucan degradation to destruct cell walls, and ultimately reduce postharvest decay caused by A. niger in grapes. This study evaluated the potential of CsA as a grape preservative and provided new insights into the mechanisms underlying the molecular response in A. niger with the treatment of CsA.

Acuminatums E and F, two new cyclic lipopeptides from Fusarium lateritium HU0053 and their antifungal activity.

Two new cyclic lipopeptides, acuminatums E (1) and F (2), together with four known cyclic lipopeptides, acuminatums A-D (3-6) were isolated from the corn culture of endophytic Fusarium lateritium HU0053. Their structures were elucidated by spectroscopic and advanced Marfey's amino acid analysis. All compounds were found to exhibit antifungal activities against Penicillium digitatum. Acuminatum F (2), a new cyclic lipopeptide containing an unusual 3, 4-dihydroxy-phenylalanine unit exhibited the strongest antifungal activities with inhibition zone of 6.5 mm at the dose of 6.25 µg. Therefore, acuminatum F might be a potential environmental-friendly preservative for citrus fruits.

Coronavirus Disease 2019-Related Multisystem Inflammatory Syndrome in Children: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to describe the clinical symptoms, laboratory findings, treatment, and outcomes of coronavirus disease 2019-related multisystem inflammatory syndrome in children to provide a reference for clinical practice. METHODS: We employed a literature search of databases such as PubMed, Web of Science, EMBASE, and Johns Hopkins University for articles on COVID-19-related multisystem inflammatory syndrome in children published between April 1, 2020, and January 15, 2021. High-quality articles were selected for analysis on the basis of their quality standard scores. Using R3.6.3 software, meta-analyses of random- or fixed-effects models were used to determine the prevalence of comorbidities. Subgroup analysis was also performed to determine heterogeneity. RESULTS: A total of 57 articles (2,290 pediatric patients) were included in the study. Clinical Manifestations. :ncidences of fever, gastrointestinal symptoms, respiratory symptoms, and musculoskeletal symptoms (myalgias or arthralgias) were 99.91% (95% CI: 99.67-100%), 82.72% (95% CI: 78.19-86.81%), 53.02% (45.28-60.68%), and 14.16% (95% CI: 8.4-21.12%), respectively. The incidences of rash, conjunctival injection, lymphadenopathy, dry cracked lips, neurologic symptoms (headache, altered mental status, or confusion), swollen hands and feet, typical Kawasaki disease, and atypical Kawasaki disease were 59.34% (95% CI: 54.73-63.87%), 55.23% (95% CI: 50.22-60.19%), 27.07% (95% CI: 19.87-34.93%), 46.37% (95% CI: 39.97-52.83%), 28.87% (95% CI: 22.76-35.40%), 28.75% (95% CI: 21.46-36.64%), 17.32% (95% CI: 15.44-19.29%), and 36.19% (95% CI: 21.90-51.86%), respectively. The incidences of coronary artery dilation, aneurysm, pericardial effusion, myocarditis, myocardial dysfunction, high troponin, and N-terminal pro-B-type natriuretic peptide were 17.83%, 6.85%, 20.97%, 35.97%, 56.32%, 76.34%, and 86.65%, respectively. The incidences of reduced lymphocytes, thrombocytopenia, hypoalbuminemia, elevated C-reactive protein, ferritin, LDH, interleukin-6, PCT, and FIB were 61.51%, 26.42%, 77.92%, 98.5%, 86.79%, 80.59%, 89.30%, 85.10%, and 87.01%, respectively. PICU Hospitalization Rate and Mortality. The incidences of PICU hospitalization or with shock were 72.79% and 55.68%, respectively. The mortality rate was 1.00%. Conclusion and Relevance. PICU hospitalization and shock rates of multisystem inflammatory syndrome in children associated with COVID-19 were high, and its cumulative multiorgans and inflammatory indicators are increased, but if treated in time, the mortality rate was low.

Prevalence of mcr-1 in Colonized Inpatients, China, 2011-2019.

In response to the spread of colistin resistance gene mcr-1, China banned the use of colistin in livestock fodders. We used a time-series analysis of inpatient colonization data from 2011-2019 to accurately reveal the associated fluctuations of mcr-1 that occurred in inpatients in response to the ban.

Unexpected HbA1c results in the presence of three rare hemoglobin variants.

Hemoglobin (Hb) variants, characterized by structural abnormalities in the globin chains, are among the most common inherited disorders. It has been shown that Hb variant remains an important cause of erroneous HbA1c results. Thus, it is important to be aware of the extent of the interference of each Hb variant encountered to avoid reporting unreliable results. However, the effects of many types of Hb variants on the measurement of HbA1c remain unclear. Here, we describe three rare Hb variants, Hb J-Tashikuergan [HBA2: c.59 C > A], Hb Pyrgos [HBB: c.251G > A], and Hb Hope [HBB: c.410 G > A], which lead to extremely high values (>25%) determined by Variant II Turbo 2.0. We further investigated their effects on HbA1c measurement by an HPLC system (Bio-Rad D100), a CE system (Sebia Capillarys 3 TERA), a boronate affinity chromatography system (Premier Hb9210), and an immunoassay method (Roche Diagnostics), and found that these Hb variants severely interfered with HbA1c measurement by Variant II Turbo 2.0 and Bio-Rad D100. This study demonstrates that patients with abnormally high HbA1c levels should be highly suspected of carrying Hb variants. When the HbA1c results are considered unreliable, other indicators such as glycated albumin may be a possible alternative to HbA1c in diabetic patients.

Retracted: lncRNA IGF2-AS Promotes Cell Proliferation, Migration, and Invasion of Gastric Cancer by Modulating miR-937/EZH2 Axis.

The article entitled, "lncRNA IGF2-AS Promotes Cell Proliferation, Migration, and Invasion of Gastric Cancer by Modulating miR-937/EZH2 Axis," by Zizi Li, Zhanyu Li, Zhijuan Zhong, Jianhui Zhou, Shenhao Huang, Wenying Zhou, and Jianfeng Xu (Cancer Biother Radiopharm epub 25 May 2020; Doi: 10.1089/cbr.2019.3275) is being officially retracted from the literature. The Editor-in-Chief of Cancer Biotherapy and Radiopharmaceuticals (CBR) received an email from the corresponding author of the article, Wenying Zhou, on September 7, 2020, indicating: "…this manuscript should no longer be published [because of] information from our superior and also after discussion with my research team, we want to repeat our experiment and then revise the [manuscript]. Our team has a lot of controversy about these results. In order to ensure the quality of the data and not to mislead readers, we decided to [retract] the manuscript. We will be more rigorous in our further study." The editor requested further information about precisely which data could not be reproduced, to which Dr. Wenying Zhou responded: "…we found that the results of Figure 4B and 4C, Figure 5A and 5B could not be repeated. Our repeated results of Figure 4B and 4C were as follow[s]: compared with miR-NC group, there was no significant decrease of the luciferase activity in miR-937 group when cells co-transfected with EZH2 3'-UTR-WT. Our repeated results of Figure 5A and 5B were as follow[s]: miR-937 inhibited the proliferation of MNK-28 and SGC-7901 cells, but the cell proliferation had no significant change in miR-937+EZH2 group compared with miR-937+pcDNA group. These findings resulted in the uncertainty of the targeted relationship between miR-937 and EZH2. We also repeated these experiments in different environments, but they all contradict the results in the original data. So, the conclusion is very controversial. In a responsible attitude to the readers, we decide to [retract] the manuscript." The authors have extended their apologies to the Editor and to the readers of CBR. Though in the author's original email, the request was made to "withdraw" the paper, CBR has decided to fully retract it due to irreproducible data, as the journal is committed to preserving the scientific literature and the community it serves.

Involvement of Transcription Elongation Factor GreA in Mycobacterium Viability, Antibiotic Susceptibility, and Intracellular Fitness.

There is growing evidence that GreA aids adaptation to stressful environments in various bacteria. However, the functions of GreA among mycobacteria remain obscure. Here, we report on cellular consequences following deletion of greA gene in Mycobacterium spp. The greA mutant strain (ΔgreA) was generated in Mycobacterium smegmatis, Mycobacterium tuberculosis (MTB) H37Ra, and M. tuberculosis H37Rv. Deletion of greA results in growth retardation and poor survival in response to adverse stress, besides rendering M. tuberculosis more susceptible to vancomycin and rifampicin. By using RNA-seq, we observe that disrupting greA results in the differential regulation of 195 genes in M. smegmatis with 167 being negatively regulated. Among these, KEGG pathways significantly enriched for differentially regulated genes included tryptophan metabolism, starch and sucrose metabolism, and carotenoid biosynthesis, supporting a role of GreA in the metabolic regulation of mycobacteria. Moreover, like Escherichia coli GreA, M. smegmatis GreA exhibits a series of conservative features, and the anti-backtracking activity of C-terminal domain is indispensable for the expression of glgX, a gene was down-regulated in the RNA-seq data. Interestingly, the decrease in the expression of glgX by CRISPR interference, resulted in reduced growth. Finally, intracellular fitness significantly declines due to loss of greA. Our data indicates that GreA is an important factor for the survival and resistance establishment in Mycobacterium spp. This study provides new insight into GreA as a potential target in multi-drug resistant TB treatment.

Long non-coding RNA FLVCR1-AS1 sponges miR-155 to promote the tumorigenesis of gastric cancer by targeting c-Myc.

BACKGROUND: Gastric cancer (GC) is one of the most common digestive tract tumors, and a serious threat to human health. Long non-coding RNA (lncRNA) are involved in many cancers. However, the biological functions of most lncRNAs are unclear. In this study, we investigated the mechanisms by which FLVCR1-AS1 regulated GC progression. METHODS: FLVCR1-AS1 expression in GC tissues and 3 GC cell lines were measured by quantitative real-time PCR (qRT-PCR). Invasion, proliferation, and apoptosis profiles were analyzed by commercial assays to determine the biological functions of FLVCR1-AS1 in GC cells. The binding sites of micro RNA-155 (miR-155) on FLVCR1-AS1 were predicted using the miRDB program. Luciferase reporter assay was used to validate direct targeting of FLVCR1-AS1 by miR-155. The effects of FLVCR1-AS1 on expressions of c-Myc and p21 were assessed by western blotting. In vivo experiments were performed to analyze the effects of FLVCR1-AS1 on GC tumor growth. RESULTS: High expression of FLVCR1-AS1 correlated with poor clinical outcomes and prognosis in patients with GC. FLVCR1-AS1 promoted proliferation and invasion of GC cells by acting as a ceRNA to sponge miR-155. CONCLUSION: FLVCR1-AS1 acted as an oncogene in GC via FLVCR1-AS1-miR-155-c-Myc signaling and may serve as a novel therapeutic target for treatment of patients with GC.