The coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2 virus) has been sustained in China since December 2019, and has become a ...pandemic. The mental health of frontline medical staff is a concern. In this study, we aimed to identify the factors influencing medical worker anxiety in China during the COVID-19 outbreak. We conducted a cross-sectional study to estimate the prevalence of anxiety among medical staff in China from 10 February 2020 to 20 February 2020 using the Zung Self-rating Anxiety Scale (SAS) to assess anxiety, with the criteria of normal (⩽49), mild (50-59), moderate (60-70) and severe anxiety (⩾70). We used multivariable linear regression to determine the factors (e.g. having direct contact when treating infected patients, being a medical staff worker from Hubei province, being a suspect case) for anxiety. We also used adjusted models to confirm independent factors for anxiety after adjusting for gender, age, education and marital status. Of 512 medical staff in China, 164 (32.03%) had had direct contact treating infected patients. The prevalence of anxiety was 12.5%, with 53 workers suffering from mild (10.35%), seven workers suffering from moderate (1.36%) and four workers suffering from severe anxiety (0.78%). After adjusting for sociodemographic characteristics (gender, age, education and marital status), medical staff who had had direct contact treating infected patients experienced higher anxiety scores than those who had not had direct contact (β value = 2.33, confidence interval (CI) 0.65-4.00; P = 0.0068). A similar trend was observed in medical staff from Hubei province, compared with those from other parts of China (β value = 3.67, CI 1.44-5.89; P = 0.0013). The most important variable was suspect cases with high anxiety scores, compared to non-suspect cases (β value = 4.44, CI 1.55-7.33; P = 0.0028). In this survey of hospital medical workers during the COVID-19 outbreak in China, we found that study participants experienced anxiety symptoms, especially those who had direct clinical contact with infected patients; as did those in the worst affected areas, including Hubei province; and those who were suspect cases. Governments and healthcare authorities should proactively implement appropriate psychological intervention programmes, to prevent, alleviate or treat increased anxiety.
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.
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.
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
= 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).
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Highlights of this study • MiR-187-3p is significantly down-regulated in HCC, and is correlated with adverse clinical features and poor prognosis of HCC patients. • MiR-187-3p can inhibit the ...metastasis of HCC cells by regulating EMT phenotype. • S100A4 is a direct downstream target of miR-187-3p, and mediated the biological function of miR-187-3p in HCC. • MiR-187-3p can be down-regulated by hypoxia, and is involved in the promoting effects of hypoxia on the metastasis and EMT of HCC cells
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses ...tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular carcinoma (HCC) remain unclear.
The expression of CASC2 and miR-367 in HCC specimens and cell lines were detected by real-time PCR. Western blotting and immunohistochemistry were carried out for detection of epithelial-to-mesenchymal transition (EMT) markers in HCC. Transwell assays were used to determine migration and invasion of HCC cells. A mouse model for lung metastasis was established to evaluated HCC metastasis in vivo. The correlation among CASC2, miR-367 and F-box and WD repeat domain containing 7 (FBXW7) were disclosed by a dual-luciferase reporter assay, RIP assay and biotin pull-down assay.
Here, CASC2 expression was significantly downregulated in HCC tissues, especially in aggressive and recurrent cases. In accordance, CASC2 underexpression was observed in HCC cell lines compared to LO2. In vitro and in vivo experiments revealed that CASC2 inhibited migration and invasion of HCC cells. Additionally, CASC2 repressed EMT process of HCC cells. Further studies demonstrated that CASC2 could function as a competing endogenous RNA (ceRNA) by sponging miR-367 in HCC cells. Functionally, gain- and loss-of-function studies showed that miR-367 promoted migration, invasion and EMT progression of HCC cells. Moreover, further investigations disclosed that FBXW7 was a downstream target of miR-367 and CASC2 prohibited EMT progression and subsequently exerted its anti-metastatic effects via CASC2/miR-367/FBXW7 axis in HCC cells. Clinically, CASC2 underexpression and miR-367 overexpression were closely correlated with the metastasis-associated clinicopathologic features. Notably, CASC2 low-expressing and miR-367 high-expressing HCC patients showed the poorest clinical outcome.
Overall, we conclude that the CASC2/miR-367/FBXW7 axis may be a ponderable and promising therapeutic target for HCC.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic ...stress may be mediated by hydrogen peroxide (H2O2). The effects of the ROS scavenger N,N′-dimethylthiourea (DMTU) on maize seed germination through endogenous H2O2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H2O2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H2O2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes (ZmAPX2 and ZmCAT2) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm−3 DMTU). We suggest the use of 200 mmol·dm−3 DMTU as an H2O2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Tuftelin1 (TUFT1), an acidic protein constituent of developing and mineralizing tooth tissues, is regulated by hypoxia and the Hedgehog signaling pathway. We investigated the role of TUFT1 in ...hepatocellular carcinoma (HCC). qRT-PCR, immunohistochemistry and western blot were employed to evaluate TUFT1 level in HCC. MTT, BrdU, 3D culture and Transwell assays were used to assess cell viability, proliferation, in vitro growth, migration, and invasion. Subcutaneous and tail vein injection models were established to investigate in vivo growth and metastasis. Chromatin immunoprecipitation was performed to assess binding of hypoxia-inducible factor 1α (HIF-1α) to TUFT1 promoter. A microRNA array was used to identify hypoxia-related microRNAs. TUFT1 was elevated in HCC, and correlated with unfavorable clinicopathologic characteristics and poor survival. TUFT1 promoted HCC cell growth, metastasis and epithelial-mesenchymal transition in vitro and in vivo via activation of Ca2+/PI3K/AKT pathway. Hypoxia induced TUFT1 expression in an HIF-1α dependent manner, and TUFT1 expression was positively correlated with HIF-1α level in HCC tissues. Hypoxiaenhanced TUFT1 expression by downregulating miR-671-5p rather than by directly promoting the binding of HIF-1α to TUFT1 promoter. MiR-671-5p interacted with the 3′-UTR of TUFT1 mRNA and subsequently inhibited TUFT1 expression. Consequently, knockdown of TUFT1 blocked the effects of hypoxia in promoting HCC progression. TUFT1 promoted the growth, metastasis and EMT of HCC cells through activating Ca2+/PI3K/AKT pathway. The hypoxic microenvironment increased the expression of TUFT1 via downregulation of miR-671-5p. TUFT1 may function as a potential therapeutic target for the intervention and treatment of HCC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
MiR-34a, a direct target of p53, has been shown to target several molecules associated with the cell cycle and cell survival pathways, and its dysregulation is implicated in cancer drug resistance or ...sensitivity in several human cancers. However, the correlation between miR-34a expression and chemoresistance has not been explored in HCC. In this study, we confirmed that miR-34a was significantly down-regulated in HCC tissues and HCC cell lines by qRT-PCR. HCC tissues with lower miR-34a expression displayed higher expression of Bcl-2 protein than those with high expression of miR-34a; therefore, an inverse correlation is evident between the miR-34a level and Bcl-2 expression. Moreover, patients with lower miR-34a expression had significantly poorer overall survival. Bioinformatics and luciferase reporter assays revealed that miR-34a binds the 3'-UTR of the Bcl-2 mRNA and represses its translation. Western blotting analysis and qRT-PCR confirmed that Bcl-2 is inhibited by miR-34a overexpression. Functional analyses indicated that the restoration of miR-34a reduced cell viability, promoted cell apoptosis and potentiated sorafenib-induced apoptosis and toxicity in HCC cell lines by inhibiting Bcl-2 expression. This study is the first to demonstrate that miR-34a induces sensitivity to the anti-tumor effect of sorafenib in human HCC cells, suggesting a potential role of miR-34a in the treatment of HCC.
Identification of humic-like substances (HULIS) structures and components is still a major challenge owing to their chemical complexity. This study first employed a complementary method with the ...combination of two-dimensional gas chromatography–time-of-flight mass spectrometry and liquid chromatography–quadrupole-time-of-flight mass spectrometry to address low-polarity and polar components of HULIS in PM2.5 (particulate matter with an aerodynamic diameter less than 2.5 μm), respectively. The combination method showed a significant correlation in identifying overlapping species and performed well in uncovering the chemical complexity of HULIS. A total of 1246 compound species in HULIS (65.6–81.0% for each sample), approximately 1 order of magnitude more compounds than that reported in previous studies, were addressed in PM2.5 collected in real-world household biomass and coal combustion. Aromatics were the most abundant compounds (37.4–64.1% in biomass and 34.5–70.0% in coal samples) of the total mass in all HULIS samples according to carbon skeleton determination, while the major components included phenols (2.6–21.1%), ketones (6.0–17.1%), aldehydes (1.1–6.8%), esters (2.9–20.0%), amines/amides (3.2–8.5%), alcohols (3.8–17.0%), and acids (4.7–15.1%). Among the identified HULIS species, 11–36% mass in biomass and 11–41% in coal were chromophores, while another 22–35 and 23–29% mass were chromophore precursors, respectively. The combination method shows promise for uncovering HULIS fingerprinting.
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IJS, KILJ, NUK, PNG, UL, UM
OBJECTIVES:Existing studies evaluating the accuracy of heparin-binding protein for the diagnosis of sepsis have been inconsistent. We conducted a systematic review and meta-analysis to assess the ...totality of current evidence regarding the utility of heparin-binding protein to diagnose sepsis in patients with presumed systemic infection.
DATA SOURCE:PubMed, Embase, the China National Knowledge infrastructure, and WangFang electronic database were searched from inception to December of 2019.
STUDY SELECTION:Two independent reviewers identified eligible studies. Cohort and case-control studies, which measured serum levels of heparin-binding protein among adult patients with suspected sepsis, were eligible for inclusion.
DATA EXTRACTION:Two reviewers independently extracted data elements from the selected studies. A bivariate random-effects meta-analysis model was used to synthesize the prognostic accuracy measures. Risk of bias of studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2 tool.
DATA SYNTHESIS:We identified 26 studies with 3,868 patients in the meta-analysis. Heparin-binding protein had a pooled sensitivity of 0.85 (95% CI, 0.79–0.90) and a pooled specificity of 0.91 (95% CI, 0.82–0.96) for the diagnosis of sepsis. There was low heterogeneity between the studies (I = 12%), and no evidence of publication bias was detected. Heparin-binding protein had a higher sensitivity and specificity when compared with procalcitonin (0.75 95% CI, 0.62–0.85 and 0.85 95% CI, 0.73–0.92) as well as C-reactive protein (0.75 95% CI, 0.65–0.84 and 0.71 95% CI, 0.63–0.77). Serial measurements of heparin-binding protein also showed that heparin-binding protein levels rose significantly at least 24 hours before a diagnosis of sepsis.
CONCLUSIONS:The diagnostic ability of heparin-binding protein is favorable, demonstrating both high sensitivity and specificity in predicting progression to sepsis in critically ill patients. Future studies could assess the incremental value that heparin-binding protein may add to a multimodal sepsis identification and prognostication algorithm for critically ill patients.
Accumulating evidence confirm that aberrant microRNAs (miRNAs) expression contributes to hepatocellular carcinoma (HCC) development and progression. Previous study reported that miR-1468 showed an ...up-regulated tendency and might be a potential prognostic biomarker in HCC samples derived from TCGA database. However, the role of miR-1468 and its underlying mechanisms involved in the growth and metastasis of HCC remain poorly investigated.
CCK-8, EdU, colony formation and flow cytometry were used to determine proliferation, cell cycle progression and apoptosis of HCC cells in vitro. The subcutaneous tumor model in nude mice was established to detect tumor growth of HCC in vivo. The direct binding of miR-1468 to 3'UTR of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 2 (CITED2) and Up-frameshift protein 1 (UPF1) was confirmed by luciferase reporter assay.
Here, we demonstrated that miR-1468 expression was up-regulated in HCC tissues and cell lines. Clinical analysis revealed that increased miR-1468 level was significantly correlated with malignant prognostic features and shorter survival. Gain- and loss-of-function experiments indicated that miR-1468 promoted cell proliferation, colony formation, cell cycle progression and induced apoptosis of HCC cells in vitro and in vivo. Moreover, CITED2 and UPF1 were identified as direct downstream targets of miR-1468 in HCC cells, and mediated the functional effects of miR-1468 in HCC, resulting in peroxisome proliferator-activated receptor-γ (PPAR-γ)/AKT signaling activation. In clinical samples of HCC, miR-1468 inversely correlated with the levels of CITED2 and UPF1, which were confirmed to be down-regulated in HCC. Restoration of CITED2 or UPF1 expression at least partially abolished the biological effects of miR-1468 on HCC cells. Moreover, alteration of PPAR-γ or AKT phosphorylation could reverse the function of miR-1468 in HCC.
Taken together, this research supports the first evidence that miR-1468 plays an oncogenic role in HCC via activating PPAR-γ/AKT pathway by targeting CITED2 and UPF1, and represents a promising therapeutic strategy for HCC patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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