Background: SHP2 regulates cancer development and progression.Results: SHP2 promotes TGFβ1-induced EMT requiring its phosphatase activity. PTP and N-SH2 domains of SHP2 interact with Hook1, which negatively regulates TGFβ1-induced EMT.Conclusion: SHP2-Hook1 complex regulates TGFβ1-induced EMT.Significance: SHP2 plays important roles in tumor metastases due to promoting EMT in cancer cells.
We used quality control circles (QCC) followed by the PDCA Deming cycle and analyzed the application of QCC to the sustained improvement of a medical institution in Zhejiang province. Analyses of the tangible and intangible achievements of QCC revealed that the achievement indices for reductions in internal errors, reductions in costs, improvements in the degree of patient satisfaction, improvements in work quality, and improvements in economic performance were 109.84% ± 16.47%, 135.04% ± 50.33%, 126.26% ± 53.69%, 100.58% ± 22.83%, and 104.07% ± 5.45%, respectively. The improvements in these areas were 61.12% ± 13.2%, 60.47% ± 28.91%, 34.41% ± 22.96%, 49.22% ± 25.39%, and 73.70% ± 5.24%, respectively. The intangible achievements were reflected as follows: 5% of QCC members showed an activity growth value of 1–2 points, 83% 1–2 points, 12% more than 2 points. As a result, QCC activity showed prominent results in fostering long-lasting improvement in the quality of medical institutions in terms of both tangible and intangible factors. In short, QCC can be used as an effective tool to improve medical quality.
Transforming growth factor β (TGFβ) signaling plays an important role in regulating tumor malignancy, including in non-small cell lung cancer (NSCLC). The major biological responses of TGFβ signaling are determined by the effector proteins SMAD2 and SMAD3. However, the regulators of TGFβ-SMADs signaling are not completely revealed yet. Here, we showed that the scaffolding protein PDZ and LIM domain protein 5 (PDLIM5, ENH) critically promotes TGFβ signaling by maintaining SMAD3 stability in NSCLC. Firstly, PDLIM5 was highly expressed in NSCLC compared with that in adjacent normal tissues, and high PDLIM5 expression was associated with poor outcome. Knockdown of PDLIM5 in NSCLC cells decreased migration and invasion in vitro, and lung metastasis in vivo. In addition, TGFβ signaling and TGFβ-induced epithelial-mesenchymal transition (EMT) was repressed by PDLIM5 knockdown. Mechanistically, PDLIM5 knockdown resulted in a reduction of SMAD3 protein levels. Overexpression of SMAD3 reversed the TGFβ-signaling-repressing and anti-migration effects induced by PDLIM5 knockdown. Notably, PDLIM5 interacted with SMAD3 but not SMAD2, and competitively suppressed the interaction between SMAD3 and its E3 ubiquitin ligase STUB1. Therefore, PDLIM5 protected SMAD3 from STUB1-mediated proteasome degradation. STUB1 knockdown restored SMAD3 protein levels, cell migration and invasion in PDLIM5-knockdown cells. Collectively, our findings indicate that PDLIM5 is a novel regulator of basal SMAD3 stability, with implications for controlling TGFβ signaling and NSCLC progression.
Abstract:Objective: XRCC1 polymorphism is a research hotpot in individual treatment for non-small cell lung cancer (NSCLC). To obtain the association between XRCC1 polymorphism and clinical outcome of platinum-based treatment for NSCLC, a meta-analysis was conducted. Methods: Databases including PubMed, Embase, Cochrane, and Chinese National Knowledge Infrastructure (CNKI) were searched for publications that met the inclusion criteria. A fixed effect model was used to estimate pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) for the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC. A chi-squared-based Q-test was used to test the heterogeneity hypothesis. Egger's test was used to check publication bias. Results: Seventeen published case-control studies that focus on the association between XRCC1 Arg399Gln and response or survival of platinum-based treatment for advanced NSCLC in 2 256 subjects were included in this meta-analysis, of whom 522 were AA genotypes (23.2% frequency), 916 AG genotypes (40.6% frequency), and 818 GG genotypes (36.2% frequency). The overall response rate (ORR) was 45.2% (110/243) for AA genotype patients, 29.9% for AG genotype (73/244), and 30.7% for GG genotype (124/403). The heterogeneity test did not show any heterogeneity and the Egger's test did not reveal an obvious publication bias among the included studies. The meta-analysis indicated that AA genotype patients presented higher response rates toward platinum drug treatment compared with G model (GG+GA) patients (GG vs. AA model: OR=0.489, P=0.021; AG vs. AA model: OR=0.608, P=0.026; GA+AA vs. GG model: OR=1.259, P=0.135; GG+GA vs. AA model: OR=0.455, P=0.0001). However, no evidence validates XRCC1 associates with the survival following platinum drug therapy. Conclusions: Our meta-analysis suggested that XRCC1 Arg399Gln is related with the sensitivity of NSCLC patients to platinum-based treatment. AA genotype patients present more desirable curative effectiveness compared with other patients.
This study investigated the impacts of risk perception of COVID-19 on anxiety and depression symptoms among hospital pharmacists in China. We conducted a cross-sectional study with hospital pharmacists during the COVID-19 pandemic in China. Some 4,219 hospital pharmacists completed an online survey including demographic questions, risk perception of COVID-19, General Anxiety Disorder-7, Patient Health Questionnaire-9, and Positive and Negative Affect Schedule. Multivariate regression and mediation analyses were conducted. The results indicated that 41.9% and 29.4% of hospital pharmacists experienced mild to severe levels of anxiety and depression symptoms, respectively. In older age, a higher level of risk perception of COVID-19, and negative affect experience were risk factors, whereas positive affect experience was a protective factor for anxiety and depression symptoms among pharmacists. Experience of positive and negative affect mediated the relationship between risk perception of COVID-19 and anxiety and depression among hospital pharmacists in China. Timely mental health services need to be provided for hospital pharmacists during the COVID-19 pandemic.
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