Objective: To provide clinical management guidelines for novel coronavirus in pregnancy. Methods:On February 5, 2020, a multidisciplinary teleconference comprising Chinese physicians and researchers was held and medical management strategies of COVID-19 infection in pregnancy were discussed. Results:Ten key recommendations were provided for the management of COVID-19 infections in pregnancy. Conclusion:Currently, there is no clear evidence regarding optimal delivery timing, the safety of vaginal delivery, or whether cesarean delivery prevents vertical transmission at the time of delivery; therefore, route of delivery and delivery timing should be individualized based on obstetrical indications and maternal-fetal status.
The clinical picture of severe acute respiratory syndrome (SARS) is characterized by an over-exuberant immune response with lung lymphomononuclear cells infilteration and proliferation that may account for tissue damage more than the direct effect of viral replication. To understand how cells response in the early stage of virus-host cell interaction, in this study, a purified recombinant S protein was studied for stimulating murine macrophages (RAW264.7) to produce proinflammatory cytokines (IL-6 and TNF-alpha) and chemokine IL-8. We found that direct induction of IL-6 and TNF-alpha release in the supernatant in a dose-, time-dependent manner and highly spike protein-specific, but no induction of IL-8 was detected. Further experiments showed that IL-6 and TNF-alpha production were dependent on NF-kappaB, which was activated through I-kappaBalpha degradation. These results suggest that SARS-CoV spike protein may play an important role in the pathogenesis of SARS, especially in inflammation and high fever.
A novel coronavirus (CoV) has recently been identified as the aetiological agent of severe acute respiratory syndrome (SARS). Nucleocapsid (N) proteins of the Coronaviridae family have no discernable homology, but they share a common nucleolar-cytoplasmic distribution pattern. There are three putative nuclear localization signal (NLS) motifs present in the N. To determine the role of these putative NLSs in the intracellular localization of the SARS-CoV N, we performed a confocal microscopy analysis using rabbit anti-N antisera. In this report, we show that the wild type N was distributed mainly in the cytoplasm. The N-terminal of the N, which contains the NLS1 (aa38-44), was localized to the nucleus. The C-terminus of the N, which contains both NLS2 (aa257-265) and NLS3 (aa369-390) was localized to the cytoplasm and the nucleolus. Results derived from analysis of various deletion mutations show that the region containing amino acids 226-289 is able to mediate nucleolar localization. The deletion of two hydrophobic regions that flanked the NLS3 recovered its activity and localized to the nucleus. Furthermore, deletion of leucine rich region (220-LALLLLDRLNRL) resulted in the accumulation of N to the cytoplasm and nucleolus, and when fusing this peptide to EGFP localization was cytoplasmic, suggesting that the N may act as a shuttle protein. Differences in nuclear/nucleolar localization properties of N from other members of coronavirus family suggest a unique function for N, which may play an important role in the pathogenesis of SARS.
Background: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in women worldwide. Recently, studies have been published with inconsistent findings regarding whether sarcopenia is a risk factor for mortality in breast cancer patients. Therefore, the aim of this systematic review and meta-analysis was to systematically assess and quantify sarcopenia as a risk factor for mortality in breast cancer patients. Methods: In a systematic literature review of PubMed, EMBASE, and the Cochrane CENTRAL Library, we searched for observational studies written in English (from database inception until April 30, 2019) that reported an association between sarcopenia and breast cancer in women who were 18 years or older. Results: A total of six studies (5497 participants) were included in this meta-analysis. Breast cancer patients with sarcopenia were associated with a significantly higher risk of mortality, compared to breast cancer patients without sarcopenia (pooled HR-hazard ratio = 1.71, 95% CI: 1.25-2.33, I 2 = 59.1%). In addition, the results of age subgroup analysis showed that participants younger than 55 years with sarcopenia had a lower risk of mortality than participants aged 55 years and older with sarcopenia (pooled HR = 1.46, 95% CI: 1.24-1.72 versus pooled HR = 1.99, 95% CI: 1.05-3.78), whereas both have an increased risk of mortality compared to non-sarcopenic patients. Subgroup analyses regarding stage at diagnosis revealed an increased risk of mortality in non-metastatic patients compared to participants without sarcopenia (pooled HR = 1.91, 95% CI: 1.32-2.78), whereas the association was not significant in metastatic breast cancer patients. Other subgroup analyses were performed using different follow-up periods (> 5 years versus ≤5 years) and the results were different (pooled HR = 1.81, 95% CI: 1.23-2.65 versus pooled HR = 1.70, 95% CI: 0.80-3.62). Conclusions: The present study found that sarcopenia is a risk factor for mortality among female early breast cancer patients. It is imperative that more research into specific interventions aimed at treating sarcopenia be conducted in the near future in order to provide evidence which could lead to decreased mortality rates in breast cancer patients.
Severe acute respiratory syndrome coronavirus (SARS-CoV) infects many organs, such as lung, liver, and immune organs and causes life-threatening atypical pneumonia, SARS causes high morbidity and mortality rates. The molecular mechanism of SARS pathogenesis remains elusive. Inflammatory stimuli can activate IkappaB kinase (IKK) signalsome and subsequently the nuclear factor kappa B (NF-kappaB), which influences gene expression of cyclooxygenase-2 (Cox-2) along with other transcription factors. In this work, we found that the membrane (M) protein of SARS-CoV physically interacted with IKKbeta using a co-immunoprecipitation assay (IPA). Expression of M suppressed tumor necrosis factor alpha (TNF-alpha) induced NF-kappaB activation using a luciferase reporter assay. Further investigation showed M protein suppressed Cox-2 expression using a luciferase reporter gene assay, RT-PCR and Western blot analysis. The carboxyl terminal of M protein was sufficient for the M protein function. Together, these results indicate that SARS-CoV M suppresses NF-kappaB activity probably through a direct interaction with IKKbeta, resulting in lower Cox-2 expression. Suppression of NF-kappaB activity and Cox-2 expression may contribute to SARS pathogenesis.
Objectives: To assess and quantify sarcopenia as a risk for falls among community-dwelling older people and nursing home older persons. Methods: Prospective cohort studies that evaluated the association between sarcopenia and falls in older adults were identified via a systematic literature search of Medline (via Ovid), PubMed, EMBASE, and the Cochrane CENTRAL Library from database inception until October 15, 2018, in English and Chinese. Results: 10 studies (10,073 participants) were included in the meta-analysis. Among older adults, having sarcopenia was significantly associated with a higher risk of falls, compared to older adults without sarcopenia (pooled OR-odds ratio ¼ 1.52, 95% CI-confidence interval: 1.32e1.77, I 2 ¼ 39.1%). In addition, the results of subgroup analysis indicated that male participants with sarcopenia had a higher risk of falls than mixed gender participants with sarcopenia (pooled OR ¼ 1.72, 95% CI: 1.36e2.18 versus pooled OR ¼ 1.41, 95% CI: 1.16e1.70). Other subgroup analyses were conducted using different study follow-up periods (>1 year versus 1 year) (pooled OR 1.63, 95% CI: 1.38e1.92 versus 1.20, 95% CI: 0.87e1.65). In addition, community-dwelling older people with sarcopenia was significantly increase risk of fall, compared with non-sarcopenia (pooled OR ¼ 1.69, 95% CI: 1.43e2.00), whereas it was not found among nursing home residents (pooled OR ¼ 1.12, 95% CI: 0.84e1.51). Furthermore, sarcopenia definition subgroup analysis found that older adults with sarcopenia increase the risk of falls when using EWGSOP (pooled OR ¼ 1.43, 95% CI: 1.19e1.72), FNIH (pooled OR ¼ 1.82, 95% CI: 1.39e2.37), AWGS (pooled OR ¼ 7.68, 95% CI: 1.41e41.80), respectively. Conclusion: The present study found that sarcopenia is a risk factor for falls among community-dwelling older people, but not among nursing home older persons. Future research is needed to provide evidence for specific interventions aimed at treating sarcopenia and preventing falls among older adults dwelling in the community.
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