High expression of MMP19 is associated with poor prognosis in patients with colorectal cancer.

BACKGROUND: Matrix metalloproteinase 19 (MMP19) is a member of zinc-dependent endopeptidases, which have been involved in various physiological and pathological processes. Its expression has been demonstrated in some types of cancers, but the clinical significance of MMP19 in colorectal cancer (CRC) has not been reported. Thus, we aimed to analyze the clinical significance of MMP19 in CRC in present study. METHODS: The expression of MMP19 was first explored in The Cancer Genome Atlas (TCGA) cohort, and then validated in the GSE39582 cohort and our own database. Clinicopathological features and survival rate were also investigated. RESULTS: MMP19 was found to be a predictor for overall survival (OS) in both univariate (hazard ratio [HR]: 1.449, 95% confidence interval [CI]: 1.108-1.893, P = 0.007) and multivariate survival analyses (HR: 1.401, 95% CI: 1.036-1.894, P = 0.028) in the TCGA database. MMP19 was further validated as an independent factor for recurrence free survival in the GSE39582 database by both univariate analysis (HR: 2.061, 95%CI: 1.454-2.921, P < 0.001) and multivariate analysis (HR = 1.470, 95% CI: 1.025-2.215, P = 0.032). In an in-house cohort, MMP19 was significantly upregulated in CRC tissues when compared with their adjacent normal controls (P < 0.001). Ectopic MMP19 expression was positively associated with lymph node metastases (P = 0.029), intramural vascular invasion (P = 0.015) and serum carcinoembryonic antigen levels (P = 0.045). High MMP19 expression correlated with a shorter OS (HR = 5.595; 95% CI: 2.573-12.164; P < 0.001) and disease free survival (HR = 4.699; 95% CI: 2.461-8.974; P < 0.001) in multivariate cox regression analysis. CONCLUSIONS: Expression of MMP19 was upregulated in CRC. High expression of MMP19 was determined to be an independent and poor prognostic factor in CRC. These results suggest that MMP19 may be a good biomarker for CRC.

In situ assembly of one-dimensional Pt@ZnO nanofibers driven by a ZIF-8 framework for achieving a high-performance acetone sensor.

To obtain a high-performance gas sensor, it is essential to ingeniously design sensing materials containing the features of high catalytic performance, abundant oxygen vacancies, and splendid grain dispersibility through a simple method. Inspired by the fact that ZIF-8 contains semiconductor metal atoms, well-arranged ZnO nanoparticle (NP)-in situ assembled one-dimensional nanofibers (NFs) are obtained by one-step electrospinning. By incorporating Pt NPs into the cavity of ZIF-8 NPs, well-dispersed Pt@ZnO NPs driven by Pt@ZIF-8 composites are obtained after annealing. The well-arranged Pt@ZnO NP-assembled NFs not only exhibit abundant oxygen vacancies but also avoid the self-aggregation of ZnO and Pt NPs. Meanwhile, the small Pt NPs could improve the catalytic effect in return. Therefore, the gas sensor fabricated based on the above materials exhibits an acetone sensitivity of 6.1 at 370 °C, compared with pristine ZnO NFs (1.6, 5 ppm). Moreover, the well-arranged Pt@ZnO NP-assembled NFs show exceptional sensitivity to acetone with a 70.2 ppb-level detection limit in theory. The synergistic advantages of the designed sensing material open up new possibilities for non-invasive disease diagnosis.

Hepatocyte ferroptosis contributes to anti-tuberculosis drug-induced liver injury: Involvement of the HIF-1α/SLC7A11/GPx4 axis.

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is a common serious adverse event observed during the clinical treatment of tuberculosis. However, the molecular mechanisms underlying ATB-DILI remain unclear. A recent study has indicated that ferroptosis and lipid peroxidation may be involved in liver injury. Therefore, this study aimed to investigate the role of ferroptosis in the molecular mechanisms underlying ATB-DILI. Our results showed that anti-TB drugs induced hepatocyte damage in vivo and in vitro and inhibited BRL-3A cell activity in a dose-dependent manner, accompanied by increased lipid peroxidation and reduced antioxidant levels. Moreover, ACSL4 expression and Fe2+ concentration significantly increased following anti-TB drug treatment. Interestingly, anti-TB drug-induced hepatocyte damage was reversed by ferrostatin-1 (Fer-1, a specific ferroptosis inhibitor). In contrast, treatment with erastin (a ferroptosis inducer) resulted in further elevation of ferroptosis indicators. Additionally, we also found that anti-TB drug treatment inhibited HIF-1α/SLC7A11/GPx4 signaling in vivo and in vitro. Notably, HIF-1α knockdown significantly enhanced anti-TB drug-induced ferroptotic events and the subsequent exacerbation of hepatocyte damage. In conclusion, our findings indicated that ferroptosis plays a crucial role in the development of ATB-DILI. Furthermore, anti-TB drug-induced hepatocyte ferroptosis was shown to be regulated by HIF-1α/SLC7A11/GPx4 signaling. These findings shed new light on the mechanisms underlying ATB-DILI and suggest novel therapeutic strategies for this disease.

The Impact of COVID-19 Epidemic on Tuberculosis Reports Among Students - Guizhou Province, China, 2020.

What is already known about this topic?: In 2020, the implementation of non-medical interventions during the coronavirus disease 2019 (COVID-19) epidemic has created a negative impact on tuberculosis (TB) control. It is unclear if the prevalence of TB among students in Guizhou Province was also affected. What is added by this report?: Among TB cases, the proportion of student TB patients was 19.91% in the back-to-school period in 2020, which was higher than the 13.37% registered in 2017-2019, but this decreased in the COVID-19 pandemic period. The time interval between symptom onset and care-seeking of the student TB patients was the shortest in the back-to-school and physical check-up periods. What are the implications for public health practice?: TB active screening was effective for timely detection and diagnosis of TB among students, which could prevent TB outbreaks in schools.

The KLF14 Transcription Factor Regulates Glycolysis by Downregulating LDHB in Colorectal Cancer.

The Krüppel-like transcription factor 14 (KLF14) is a critical regulator of a wide array of biological processes. However, the role of KLF14 in colorectal cancer (CRC) isn't fully investigated. This study aimed to explore the clinicopathological significance and potential role of KLF14 in the carcinogenesis and progression of CRC. A tissue microarray consisting of 185 samples from stage I-III CRC patients was adopted to analyze the correlation between KLF14 expression and clinicopathological parameters, as well as overall survival (OS) and disease-free survival (DFS). The underlying mechanisms of altered KLF14 expression on glycolysis were studied using in vitro and patients' samples. The results showed that KLF14 expression was downregulated in CRC than their normal controls. Low KLF14 expression correlated with advanced T stage (P< 0.001) and N stage (P= 0.040), and larger tumor size (P= 0.008). Lost KLF14 expression implied shorter OS and DFS after colectomy in both univariate and multivariate survival analysis (P<0.05). Experimentally, restore KLF14 expression significantly decreased the rate of glycolysis both in vitro and in patients' sample. Mechanically, KLF14 regulated glycolysis by downregulating glycolytic enzyme LDHB. Collectively, KLF14 is a novel prognostic biomarker for survival in CRC, and downregulation of KLF14 in CRC prompts glycolysis by target LDHB. Hence, KLF14 could constitute potential prognostic predictors and therapeutic targets for CRC.

NOTCH4 Is a Novel Prognostic Marker that Correlates with Colorectal Cancer Progression and Prognosis.

Notch family plays vital role in carcinogenesis and progression of various cancer, however, its clinical significance and prognostic value in colorectal cancer isn't fully investigated. In present study, we first investigated the NOTCH4 expression in The Cancer Genome Atlas (TCGA) (n=361) and GSE39582 (n=474) database and then validated with our own database (n=248). The transcriptional and protein levels of NOTCH4 were evaluated by RT-PCR and immunohistochemistry study, respectively. Univariate and multivariate survival analyses were performed to explore the relationship between various prognostic factors and survival outcomes. In the univariate analysis, NOTCH3 and NOTCH4 were significantly correlated with prognosis in TCGA and GSE39582 database, respectively (P<0.05). For NOTCH3 has been studied in CRC, we chosen NOTCH4 for further study. NOTCH4 mRNA was higher in liver metastases than their primary colorectal cancer or normal mucosa. Increased NOTCH4 levels significantly correlated with advanced N stage (P= 0.002), M stage (P= 0.002), lymphovascular invasion (P= 0.026), and CEA status (P= 0.030). Patients with high NOTCH4 expression had shorter 5-year disease-free survival (DFS) (HR 6.809; 95% CI 3.334-13.904; P< 0.001) and overall survival (OS) (HR 6.476; 95% CI 3.307-12.689; P<0.001) than those with low NOTCH4 expression. Multivariate survival analysis demonstrated that NOTCH4 was an independent prognostic biomarker for both DFS (HR 7.848; 95% CI 3.777-16.308; P<0.001) and OS (HR 5.323; 95% CI 2.668-10.623; P<0.001).Collectively, NOTCH4 may play critical role in colorectal cancer progression and could serve as a novel biomarker to predict survival after colectomy.

Is tuberculosis health education reaching the public in China? A cross-sectional survey in Guizhou Province.

BACKGROUND: Knowledge about tuberculosis (TB) is important for TB control, and China's national TB control guidelines emphasise TB health promotion. A 2010 national TB epidemiology survey showed that the general public had limited knowledge and awareness of TB. OBJECTIVE: To assess the level of TB knowledge after 5 years of TB health promotion in Guizhou Province, one of the regions with the highest TB burden in China. DESIGN AND SETTING: A community-based, cross-sectional survey of 10 237 residents of Guizhou Province from June to August 2015. Multiple logistic regression models were used to examine factors associated with core TB knowledge and TB health education among respondents. RESULTS: Overall, residents of Guizhou Province had inadequate knowledge of TB. The overall awareness of TB was 41.5%. Less than 30% of respondents were familiar with China's policy of free treatment for TB or knew that the disease could be cured. Factors associated with core TB knowledge included gender, age, ethnicity, education, occupation, region, and having received TB health education. Women, older adults, people employed in non-government institutions, and those living in counties with low TB burdens had little access to TB health education, whereas people with higher education levels had greater access. Respondents' sources of TB knowledge did not necessarily match their preferred channels for delivery of TB health education. CONCLUSIONS: Our findings indicate that TB health education should be further strengthened in China and other countries with a high TB burden. TB health education programmes require further formative and implementation research in order to improve programme effectiveness.