Effect of a real-time automatic nosocomial infection surveillance system on hospital-acquired infection prevention and control.

BACKGROUND: The systematic collection of valid data related to hospital-acquired infections (HAIs) is considered effective for nosocomial infection prevention and control programs. New strategies to reduce HAIs have recently fueled the adoption of real-time automatic nosocomial infection surveillance systems (RT-NISSs). Although RT-NISSs have been implemented in some hospitals for several years, the effect of RT-NISS on HAI prevention and control needs to be further explored. METHODS: A retrospective, descriptive analysis of inpatients from January 2017 to December 2019 was performed. We collected hospital-acquired infection (HAI) cases and multidrug resistant organism (MDRO) infection cases by traditional surveillance in period 1 (from January 2017 to December 2017), and these cases were collected in period 2 (from January 2018 to December 2018) and period 3 (from January 2019 to December 2019) using a real-time nosocomial infection surveillance system (RT-NISS). The accuracy of MDRO infection surveillance results over the 3 periods was examined. The trends of antibiotic utilization rates and pathogen culture rates in periods 2 and 3 were also analysed. RESULTS: A total of 114,647 inpatients, including 2242 HAI cases, were analysed. The incidence of HAIs in period 2 was significantly greater than that in period 1 (2.28% vs. 1.48%, χ2 = 61.963, p < 0.001) and period 3 (2.28% vs. 2.05%, χ2 = 4.767, p = 0.029). The incidence of five HAI sites, including respiratory infection, urinary tract infection (UTI), surgical site infection (SSI), bloodstream infection (BSI) and skin and soft tissue infection, was significantly greater in period 2 compared with period 1 (both p < 0.05) but was not significantly different from that in period 3. The incidence of hospital-acquired MDRO infections in period 3 was lower than that in period 2. The identification of MDRO infection cases using the RT-NISS achieved a high level of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV), especially in period 3 (Se = 100%, Sp = 100%, PPV = 100% and NPV = 100%). CONCLUSION: The adoption of a RT-NISS to adequately and accurately collect HAI cases is useful to prevent and control HAIs. Furthermore, RT-NISSs improve accuracy in MDRO infection case reporting, which can timely and accurately guide and supervise clinicians in implementing MDRO infection prevention and control measures.

In science we (should) trust: Expectations and compliance across nine countries during the COVID-19 pandemic.

The magnitude and nature of the COVID-19 pandemic prevents public health policies from relying on coercive enforcement. Practicing social distancing, wearing masks and staying at home becomes voluntary and conditional on the behavior of others. We present the results of a large-scale survey experiment in nine countries with representative samples of the population. We find that both empirical expectations (what others do) and normative expectations (what others approve of) play a significant role in compliance, beyond the effect of any other individual or group characteristic. In our vignette experiment, respondents evaluate the likelihood of compliance with social distancing and staying at home of someone similar to them in a hypothetical scenario. When empirical and normative expectations of individuals are high, respondents' evaluation of the vignette's character's compliance likelihood goes up by 55% (relative to the low expectations condition). Similar results are obtained when looking at self-reported compliance among those with high expectations. Our results are moderated by individuals' trust in government and trust in science. Holding expectations high, the effect of trusting science is substantial and significant in our vignette experiment (22% increase in compliance likelihood), and even larger in self-reported compliance (76% and 127% increase before and after the lockdown). By contrast, trusting the government only generates modest effects. At the aggregate level, the country-level trust in science, and not in government, becomes a strong predictor of compliance.

Identification of a novel transcript isoform of the TTLL12 gene in human cancers.

Tubulin tyrosine ligase like 12 (TTLL12), a member of the tubulin tyrosine ligase (TTLL) family, has not been completely characterized to date. It is reported that histone methylation, tubulin modifications, mitotic duration and chromosome ploidy play crucial roles in a variety of cancers, and are related to tumorigenesis and cancer progression. A recent study showed that TTLL12 may be a pseudo-enzyme which has a SET-like domain and a TTL-like domain. In the present study, we first used 3'-rapid amplification of cDNA ends (3'-RACE) to amplify the transcripts of the TTLL12 gene from a human lung cancer cell line H1299, and unexpectedly discovered a new transcript isoform characterized with an additional 108-bp nucleotide sequence inserted at the location from 902 to 903 bases of the TTLL12 coding sequence (CDS), where it also locates between exons 5 and 6. Next, utilizing RT-PCR and Sanger sequencing, we further confirmed the existence of such a new transcript isoform of TTLL12 in more human cancer cells including lung cancer cells and other cancer cells. Moreover, several lung cancer cell lines were found to display a much higher proportion of the new isoform compared with TTLL12 wild-type transcript. These results suggest that the new TTLL12 isoform may be of importance for proper maintenance of lung cancer cells. Therefore, the new isoform of TTLL12, with the inserted sequences probably acting as a disordered region, provides a novel perspective regarding TTLL12 functions in human cancers including lung cancer.

Promoting roles of the secreted frizzled-related protein 2 as a Wnt agonist in lung cancer cells.

The secreted frizzled-related protein 2 (SFRP2) plays a pivotal role in the Wnt pathway, however, it functions as an agonist or an antagonist is still controversial. We profiled SFRP2 expression in several lung cancer cell lines, and found that A549 and 95-D exhibited the lowest and the highest level of SFRP2, respectively. Then we employed the SFRP2-overexpressing plasmid and siRNA to transfect A549 and 95-D cells, respectively. Through MTT assays, we found that SFRP2 knockdown inhibited cell proliferation, and halted the 95-D cells in G1 phase of the cell cycle by downregulation of CCND1 and CDK4, indicating that SFRP2 has the ability of promoting lung cancer cell proliferation. We further checked the cell properties of migration and invasion, using wound scratch assay and Transwell assays. The data showed decreased migrated and invasive 95-D cells after SFRP2 knockdown, and the observations were the opposite in the overexpressing model, implying that SFRP2 promoted lung cancer cell invasion. Moreover, the canonical Wnt pathway was also studied through detection of ß-catenin by western blotting. In the SFRP2 overexpressing model, A549 cells presented stronger expression of ß-catenin compared with controls, while it was the opposite in 95-D cells. These results suggested that SFRP2 serves as a Wnt agonist in lung cancer cells. Together, the findings of this study implied that SFRP2 is not only an agonist of Wnt pathway, but also a cancer promoting protein for lung cancer, indicating SFRP2 as a promising therapeutic target for lung cancer treatment.

MiR-138 inhibits cell proliferation and reverses epithelial-mesenchymal transition in non-small cell lung cancer cells by targeting GIT1 and SEMA4C.

Non-small-cell lung cancer (NSCLC) is one of the most common and lethal malignant tumours worldwide with a poor 5-year survival rate. Recent studies indicated that miRNAs have been involved in the tumorigenic driver pathways in NSCLC, but the relevant molecular mechanisms are not well-understood. In this study, we investigated the biological functions and molecular mechanisms of miR-138 in human NSCLC. The effects of miR-138 on the NSCLC cell growth and epithelial-mesenchymal transition (EMT) were first examined. Then the targeting connections of miR-138 with G-protein-coupled receptor kinase-interacting protein 1 (GIT1) and semaphorin 4C (SEMA4C) were confirmed by dual luciferase reporter assays. Finally, the effects of GIT1 and SEMA4C on the NSCLC cell growth and EMT were investigated respectively. We found that the ectopic expression of miR-138 resulted in a significant inhibition of NSCLC growth and reversion of EMT. GIT1 and SEMA4C were identified as two novel targets of miR-138. Furthermore, GIT1 and SEMA4C knockdown inhibited the cell growth and reversed EMT, just like the effects of miR-138 overexpression on NSCLC cells, whereas ectopic expression of GIT1 and SEMA4C partly rescued the suppressive effects of miR-138 in NSCLC cells. These data represent a crucial step towards the understanding of the novel roles and molecular mechanism of miR-138, GIT1 and SEMA4C in NSCLC progression, which may provide some new targets or prognostic biomarkers for NSCLC treatment, thus having implications in translational oncology.

Synergistic Effects between mTOR Complex 1/2 and Glycolysis Inhibitors in Non-Small-Cell Lung Carcinoma Cells.

Cancer metabolism has greatly interested researchers. Mammalian target of rapamycin (mTOR) is dysregulated in a variety of cancers and considered to be an appealing therapeutic target. It has been proven that growth factor signal, mediated by mTOR complex 1 (mTORC1), drives cancer metabolism by regulating key enzymes in metabolic pathways. However, the role of mTORC2 in cancer metabolism has not been thoroughly investigated. In this study, by employing automated spectrophotometry, we found the level of glucose uptake was decreased in non-small-cell lung carcinoma (NSCLC) A549, PC-9 and SK-MES-1 cells treated with rapamycin or siRNA against Raptor, indicating that the inhibition of mTORC1 attenuated glycolytic metabolism in NSCLC cells. Moreover, the inhibition of AKT reduced glucose uptake in the cells as well, suggesting the involvement of AKT pathway in mTORC1 mediated glycolytic metabolism. Furthermore, our results showed a significant decrease in glucose uptake in rictor down-regulated NSCLC cells, implying a critical role of mTORC2 in NSCLC cell glycolysis. In addition, the experiments for MTT, ATP, and clonogenic assays demonstrated a reduction in cell proliferation, cell viability, and colony forming ability in mTOR inhibiting NSCLC cells. Interestingly, the combined application of mTORC1/2 inhibitors and glycolysis inhibitor not only suppressed the cell proliferation and colony formation, but also induced cell apoptosis, and such an effect of the combined application was stronger than that caused by mTORC1/2 inhibitors alone. In conclusion, this study reports a novel effect of mTORC2 on NSCLC cell metabolism, and reveals the synergistic effects between mTOR complex 1/2 and glycolysis inhibitors, suggesting that the combined application of mTORC1/2 and glycolysis inhibitors may be a new promising approach to treat NSCLC.

Epigenetic regulation of miR-129-2 and its effects on the proliferation and invasion in lung cancer cells.

MicroRNAs (miRNAs) play a pivotal role in carcinogenesis. Dysregulation of miRNAs, both oncogenic miRNAs and tumour-suppressive miRNAs, is closely associated with cancer development and progression. The levels of miRNAs could be changed epigenetically by DNA methylation in the 5' untranslated region (UTR) of pre-mature miRNAs. To investigate whether DNA methylation alters the expression of miR-129 in lung cancer, we did DNA methylation assays and found that 5' UTR region of miR-129-2 gene was absolutely methylated in both A549 and SPCA-1 lung cancer cells, but totally un-methylated in 95-D cells. The expression of miR-129 was restored by 5-Aza-2'-deoxycytidine (DAC), a de-methylation agent, in both A549 and SPCA-1 cells, resulting in attenuated cell migration and invasion ability, and decreased protein level of NF-κB, which indicates the involvement of NF-κB pathway. To further illustrate the roles of miR-129 in lung tumourigenesis, we overexpressed miR-129 in lung cancer cells by transfection of miR-129 mimics, and found arrested cell proliferation at G2/M phase of cell cycle and inhibited cell invasion. These findings strongly suggest that miR-129 is a tumour suppressive miRNA, playing important roles in the development and progression of human lung cancer.