A meta-analysis of immunogenicity and safety of two versus single-doses of influenza A (H1N1) vaccine in person living with HIV.

Purpose: Influenza vaccination of person living with HIV (PLWH) is a powerful means to tackle severe clinical outcomes. Few data on two doses of influenza vaccine in PLWH are available.Research Design: To evaluate the immunogenicity and safety of two doses of vaccine as compared with single dose in PLWH, we searched Pubmed, Embase, and web of science databases for relevant articles (January 2009 to April 2023). Pooled SMD or RR and 95% CI were calculated.Results: A total of 2436 participants from 14 studies were included. Compared to single dose influenza vaccine regimen, the pooled RR of seroprotection and seroconversion for two doses of vaccines was 1.14 (95%CI: 1.08-1.21) and 1.25 (95%CI: 1.16-1.34), respectively; the SMD of GMT was 0.42 (95%CI: 0.35, 0.49). Regarding safety, the fever risk in PLWH receiving two doses of vaccine was 3.42 fold higher than that of single dose vaccine, and the risk of myalgia had a quarter reduction. No serious vaccine-related adverse events were reported.Conclusions: Collectively, two doses of the vaccine are associated with a better immunogenicity and an acceptable safety in PLWH. Two doses of the adjuvant vaccination might be a superior vaccination regimen.nation regimen.

Molecular mechanism of Hfq-dependent sRNA1039 and sRNA1600 regulating antibiotic resistance and virulence in Shigella sonnei.

Bacillary dysentery caused by Shigella spp. is a significant concern for human health. Small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella spp. However, the specific mechanisms behind this phenomenon are still not fully understood. This study discovered two sRNAs (sRNA1039 and sRNA1600) that may be involved in bacterial resistance and virulence. By constructing deletion mutants (WT/ΔSR1039 and WT/ΔSR1600), this study found that the WT/ΔSR1039 mutants caused a two-fold increase in sensitivity to ampicillin, gentamicin and cefuroxime, and the WT/ΔSR1600 mutants caused a two-fold increase in sensitivity to cefuroxime. Furthermore, the WT/ΔSR1600 mutants caused a decrease in the adhesion and invasion of bacteria to HeLa cells (P<0.01), and changed the oxidative stress level of bacteria to reduce their survival rate (P<0.001). Subsequently, this study explored the molecular mechanisms by which sRNA1039 and sRNA1600 regulate antibiotic resistance and virulence. The deletion of sRNA1039 accelerated the degradation of target gene cfa mRNA and reduced its expression, thereby regulating the expression of pore protein gene ompD indirectly and negatively to increase bacterial sensitivity to ampicillin, gentamicin and cefuroxime. The inactivation of sRNA1600 reduced the formation of persister cells to reduce resistance to cefuroxime, and reduced the expression of type-III-secretion-system-related genes to reduce bacterial virulence by reducing the expression of target gene tomB. These results provide new insights into Hfq-sRNA-mRNA regulation of the resistance and virulence network of Shigella sonnei, which could potentially promote the development of more effective treatment strategies.

Measurable residual disease detected by flow cytometry independently predicts prognoses of NPM1-mutated acute myeloid leukemia.

Acute myeloid leukemia (AML) with NPM1 mutation is a distinct genetic entity with favorable outcomes. Nevertheless, emerging evidence suggests that NPM1-mutated AML is still a highly heterogeneous disorder. In this study, 266 patients with AML with NPM1 mutations were retrospectively analyzed to evaluate the associations between variant allele frequency (VAF) of NPM1 mutations, co-mutated genes, measurable residual disease (MRD), and patient outcomes. Multiparameter flow cytometry (MFC) and real-time quantitative polymerase chain reaction (RT-PCR) were used for monitoring MRD. Ultimately, 106 patients were included in the long-term follow-up period. Patients with high NPM1 VAF (≥ 42.43%) had poorer 2-year relapse-free survival (RFS) (55.7% vs. 70.2%, P = 0.017) and overall survival (OS) (63.7% vs. 82.0%, P = 0.027) than those with low VAF. DNMT3A mutations negatively influenced the outcomes of patients with NPM1 mutations. Patients with high DNMT3A VAF or NPM1/DNMT3A/FLT3-ITD triple mutations had shorter RFS and significantly lower OS than that in controls. After two cycles of chemotherapy, patients with positive MFC MRD results had lower RFS (MRD+ vs. MRD-:44.9% vs. 67.6%, P = 0.007) and OS (61.5% vs. 76.6%, P = 0.011) than those without positive MFC MRD results. In multivariate analysis, high NPM1 VAF (hazard ratio [HR] = 2.045; P = 0.034) and positive MRD after two cycles of chemotherapy (HR = 3.289; P = 0.003) were independent risk factors for RFS; MRD positivity after two cycles of chemotherapy (HR = 3.293; P = 0.008) independently predicted the OS of the patients. These results indicate that VAF of both NPM1 gene itself or certain co-occurring gene pre-treatment and MRD post-treatment are potential markers for restratifying the prognoses of patients AML having NPM1 mutations.

Anxiety, depression, insomnia symptoms & associated factors among young to middle-aged adults during the resurgent epidemic of COVID-19: a cross-sectional study.

The coronavirus disease 2019 (COVID-19) pandemic is a public health emergency of international concern. However, its stress on the mental health of young to middle-aged adults is largely unexplored. This study aimed to evaluate the mental health difficulties during the resurgent phase of COVID-19 among young to middle-aged adults in China. There were 1,478 participants with a median age of 26 years (IQR, 23 - 30), including 535 males (36.2%). The prevalence of anxiety, depression, and insomnia were 8.6%, 11.4%, and 13.7%, respectively. Participants aged 29 - 59 years (OR, 95% CI: 2.46, 1.23 - 4.91) and females (2.49, 1.55 - 4.01) had a higher risk of anxiety. Education status, worried level about the current COVID-19, and the level of COVID-19's impact on life were significantly associated with the prevalence of anxiety. Besides, the level of COVID-19's impact on life was positively related to the prevalence of depression and insomnia. Our study provided novel evidence of psychological difficulties among young to middle-aged adults during the resurgent stage of the COVID-19 epidemic. Psychological intervention should be continuously implemented to prevent long-term psychological comorbidities during the COVID-19 epidemic.

Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling.

Purpose: The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N6-methyladenosine (m6A) demethylase, functions as an oncogene that promotes leukemic oncogene-mediated cell transformation and leukemogenesis. Here, we investigated the role of Saikosaponin-d (SsD) in broad anti-proliferation effects in AML and evaluated the m6A demethylation activity by targeting FTO of SsD. Methods: It was examined whether and how SsD regulates FTO/m6A signaling in AML. The pharmacologic activities and mechanisms of actions of SsD in vitro, in mice, primary patient cells, and tyrosine kinase inhibitors-resistant cells were determined. Results: SsD showed a broadly-suppressed AML cell proliferation and promoted apoptosis and cell-cycle arrest both in vitro and in vivo. Mechanistically, SsD directly targeted FTO, thereby increasing global m6A RNA methylation, which in turn decreased the stability of downstream gene transcripts, leading to the suppression of relevant pathways. Importantly, SsD also overcame FTO/m6A-mediated leukemia resistance to tyrosine kinase inhibitors. Conclusion: Our findings demonstrated that FTO-dependent m6A RNA methylation mediated the anti-leukemic actions of SsD, thereby opening a window to develop SsD as an epitranscriptome-base drug for leukemia therapy.

Association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) single nucleotide polymorphism in donors with clinical outcome after allogeneic hematopoietic stem cell transplantation: a meta-analysis.

OBJECTIVE: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) polymorphisms at positions of +49 and CT60 in donors have been reported to influence clinical outcome following allogeneic hematopoietic stem cell transplantation (allo-HSCT), such as overall survival (OS), disease free survival (DFS), relapse and the risk of graft versus host disease (GVHD). However, the results still remain controversial. Thus, we conducted the first meta-analysis to get a more accurate estimation of the relationship between CTLA-4 genotype and the above end points. METHODS: PubMed, Embase, Web of science and Cochrane Library were searched to select eligible studies, data were extracted and then combined ORs/HRs together with the corresponding 95% confidence intervals (CIs) were calculated. Both the dominant and recessive models were employed to evaluate the associations between genetic variation in donor CTLA-4 and outcome after allo-HSCT. RESULTS: A total of 15 studies were included the pooled results indicated that +49 GG homozygote in donors was significantly associated with increased risk of chronic GVHD (OR=1.701, 95% CI, 1.124-2.573, P=0.012, I2=34.7%). With regard to CT60 polymorphism, donors with G allele correlated with worse OS (HR = 1.422, 95% CI, 1.080-1.872, P=0.012, I2=0%) and lower susceptibility to severe acute GVHD (HR=0.619, 95% CI, 0.426-0.899, P=0.012, I2=0%). There was no significant association between CTLA-4 polymorphism and DFS or the incidence of relapse. CONCLUSIONS: The present meta-analysis suggests that donors with CT60 G allele might be associated with worse OS but reduced severe aGVHD occurrence, while patients transplanted from donors with GG genotype at position of +49 are more likely to suffer from cGVHD.

[Clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutation].

This study was aimed to explore the clinical characteristics and therapeutic efficacy of normal karyotype AML patients with CEBPA mutations. Fifty-five de novo AML patients with normal karyotype were retrospectively analyzed with regard to frequency of CEBPA mutation, clinical characteristics and therapeutic response. The results showed that CEBPA mutation was detected in 20 patients (36.4%), among them 17 cases displayed double mutations, three cases were with single mutation. The clinical characteristics of patients with CEBPA mutation displayed as follows: 75% of AML patients with CEBPA mutation were AML-M1 and AML-M2, the hemoglobin level at newly diagnosis was higher and the platelet count at newly diagnosis time was lower than those of AML patients without CEBPA mutation [(98.30 ± 20.33) g/L vs (81.69 ± 23.74) g/L (P < 0.05); and (33.30 ± 38.27) ×10(9)/L vs (64.79 ± 61.60) ×10(9)/L (P < 0.05)]. The leukemic cells highly expressed CD7 and CD34. The therapeutic efficacy of 1 cycle for AML patients with CEBPA mutation was satisfactory (72.2%), was higher than that of patients without CEBPA mutation(68.6%), but there was no statistical significance (P > 0.05). It is concluded that AML with CEBPA mutation is more observed in AML-M1 and AML-M2, and accompanies by high level of hemoglobin and lower platelet count, expression of CD7 and CD34. Early-term therapeutic efficacy is satisfactory. The frequency of CEBPA mutation may be higher in Chinese patients with AML compared with that reported in Western world.