Quantifying the effects of cold waves on carbon monoxide poisoning: A time-stratified case-crossover study in Jinan, China

BackgroundPrevious studies have shown that carbon monoxide (CO) poisoning occurs mostly in winter and is associated with severe cold weather (e.g., ice storms, temperature drops). However, according to previous studies, the impact of low temperature on health has a delayed effect, and the existing research cannot fully reveal the delayed effect of cold waves on CO poisoning.ObjectivesThe purpose of this study is to analyze the temporal distribution of CO poisoning in Jinan and to explore the acute effect of cold waves on CO poisoning.MethodsWe collected emergency call data for CO poisoning in Jinan from 2013 to 2020 and used a time-stratified case-crossover design combined with a conditional logistic regression model to evaluate the impact of the cold wave day and lag 0–8 days on CO poisoning. In addition, 10 definitions of a cold wave were considered to evaluate the impact of different temperature thresholds and durations.ResultsDuring the study period, a total of 1,387 cases of CO poisoning in Jinan used the emergency call system, and more than 85% occurred in cold months. Our findings suggest that cold waves are associated with an increased risk of CO poisoning in Jinan. When P01, P05, and P10 (P01, P05, and P10 refer to the 1st, 5th, and 10th percentiles of the lowest temperature, respectively) were used as temperature thresholds for cold waves, the most significant effects (the maximum OR value, which refers to the risk of CO poisoning on cold wave days compared to other days) were 2.53 (95% CI:1.54, 4.16), 2.06 (95% CI:1.57, 2.7), and 1.49 (95% CI:1.27, 1.74), respectively.ConclusionCold waves are associated with an increased risk of CO poisoning, and the risk increases with lower temperature thresholds and longer cold wave durations. Cold wave warnings should be issued and corresponding protective policies should be formulated to reduce the potential risk of CO poisoning

Plasma microRNAs as potential biomarkers for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Developing minimally invasive techniques that can diagnose NSCLC, particularly at an early stage, may improve its outcome. Using microarray platforms, we previously identified 12 microRNAs (miRNAs) the aberrant expressions of which in primary lung tumors are associated with early-stage NSCLC. Here, we extend our previous research by investigating whether the miRNAs could be used as potential plasma biomarkers for NSCLC. We initially validated expressions of the miRNAs in paired lung tumor tissues and plasma specimens from 28 stage I NSCLC patients by real-time quantitative reverse transcription PCR, and then evaluated diagnostic value of the plasma miRNAs in a cohort of 58 NSCLC patients and 29 healthy individuals. The altered miRNA expressions were reproducibly confirmed in the tumor tissues. The miRNAs were stably present and reliably measurable in plasma. Of the 12 miRNAs, five displayed significant concordance of the expression levels in plasma and the corresponding tumor tissues (all r>0.850, all P<0.05). A logistic regression model with the best prediction was defined on the basis of the four genes (miRNA-21, -126, -210, and 486-5p), yielding 86.22% sensitivity and 96.55% specificity in distinguishing NSCLC patients from the healthy controls. Furthermore, the panel of miRNAs produced 73.33% sensitivity and 96.55% specificity in identifying stage I NSCLC patients. In addition, the genes have higher sensitivity (91.67%) in diagnosis of lung adenocarcinomas compared with squamous cell carcinomas (82.35%) (P<0.05). Altered expressions of the miRNAs in plasma would provide potential blood-based biomarkers for NSCLC

Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers

<p>Abstract</p> <p>Background</p> <p>Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs.</p> <p>Methods</p> <p>By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs.</p> <p>Results</p> <p>In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one.</p> <p>Conclusions</p> <p>The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.</p

Apoptosis induced by Ginkgo biloba (EGb761) in melanoma cells is Mcl-1-dependent.

Melanoma is an aggressive skin cancer. Unfortunately, there is currently no chemotherapeutic agent available to significantly prolong the survival of the most patients with metastatic melanomas. Here we report that the Ginkgo biloba extract (EGb761), one of the most widely sold herbal supplements in the world, potently induces apoptosis in human melanoma cells by disturbing the balance between pro- and anti-apoptosis Bcl-2 family proteins. Treatment with EGb761 induced varying degrees of apoptosis in melanoma cell lines but not in melanocytes. Induction of apoptosis was caspase-dependent and appeared to be mediated by the mitochondrial pathway, in that it was associated with reduction in mitochondrial membrane potential and activation of Bax and Bak. Although EGb761 did not cause significant change in the expression levels of the BH3-only Bcl-2 family proteins Bim, Puma, Noxa, and Bad, it significantly downregulated Mcl-1 in sensitive but not resistant melanoma cells, suggesting a major role of Mcl-1 in regulating apoptosis of melanoma cells induced by EGb761. Indeed, siRNA knockdown of Mcl-1 enhanced EGb761-induced apoptosis, which was associated with increased activation of Bax and Bak. Taken together, these results demonstrate that EGb761 kills melanoma cells through the mitochondrial apoptotic pathway, and that Mcl-1 is a major regulator of sensitivity of melanoma cells to apoptosis induced by EGb761. Therefore, EGb761 with or without in combination with targeting Mcl-1 may be a useful strategy in the treatment of melanoma

The threaten of typhoons to the health of residents in inland areas: a study on the vulnerability of residents to death risk during typhoon “Lekima”

Abstract Background Studies had suggested increased risk of death of residents was associated with typhoons, particularly coastal regions. However, these findings ignored the impact of inland typhoons on the health of residents, especially the indirect death risk caused by typhoons. This study aimed to investigate the acute death risk of residents during inland typhoon Lekima in Jinan, further identify vulnerable populations and areas. Methods We selected the daily death from 11 to 27th August 2019 in Jinan as case period, and conducted a time-stratified case-crossover design to match the contemporaneous data from 2016 to 2018 as control period. We used the generalized linear Poisson models to estimate the related effects of death risk during typhoon Lekima and lag days. Results During the Lekima typhoon month, there were 3,366 deaths occurred in Jinan. Compared to unexposed periods, the acute death risk of non-accidental diseases (especially circulatory diseases), female and the older adults increased significantly in the second week after the typhoon. The maximum significant effect of circulatory disease deaths, female and older adult deaths were appeared on lag9, lag9, and lag13 respectively. And the typhoon-associated RR were 1.19 (95%CI:1.05,1.34), 1.28 (95%CI:1.08,1.52), and 1.22 (95%CI:1.06,1.42) respectively. The acute death risk of residents living in TQ and CQ increased significantly on Lag2 and Lag6 after the typhoon, respectively, while those living in LX, LC, HY, JY, and SH occurred from Lag 8 to Lag 13 after the typhoon. LC lasted the longest days. Conclusions Typhoons would increase the vulnerability of residents living in Jinan which mainly occurred from the seventh day after the typhoon. Residents suffering from non-accidental diseases (circulatory diseases), female and the older adults were more vulnerable. The vulnerability of TQ and CQ occurred on Lag2 and Lag6 after typhoon Lekima, respectively, and the other areas except ZQ and PY occurred from Lag 8 to Lag 13. LC lasted the longest duration. Our findings emphasized the importance of the emergency response, which would help policymakers to identify vulnerable regions and populations accurately during typhoons and formulate the emergency response plan

EGb761 induces partially Caspase-Dependent Apoptosis in Melanoma Cells.

<p>(A) EGb761 induces caspase activation. Whole cell lysates from Mel-RM and Mel-AT cells treated with EGb761 (400 μg/ml) for the indicated time periods were subjected to Western blot analysis. The data shown are representative of three individual experiments. (B) Mel-RM and Mel-AT cells with or without treatment with EGb761 (400 μg/ml) for 16 h were subjected to flow cytometry analysis of caspase-3 activation using an antibody that specifically recognizes the activated form of caspase-3. The data shown are representative of three individual experiments. (C) Mel-RM and Mel-AT cells were pretreated with the pan-caspase inhibitor z-VAD-fmk (20 μmol/L), the caspase-3 inhibitor z-DEVD-fmk (30 μmol/L), or the caspase-9 inhibitor z-LEHD-fmk (30 μmol/L) 1h before adding EGb761 (400 μg/ml) for another 24h, respectively. Apoptosis was measured by the propidium iodide method using flow cytometry. Data are the mean ± SEM of three individual experiments. * Present p<0.05 vs control.</p

EGb761 regulates Bcl-2 family proteins expression in melanoma cells.

<p>(A) EGb761 alters the expression levels of anti- and pro-apoptotic Bcl-2 family proteins in melanoma cell lines. Whole cell lysates from Mel-RM and Mel-AT cells treated with EGb761 (400 μg/ml) for indicated time periods were subjected to Western blot analysis. The data shown are representative of three individual experiments. (B) 5% ethanol as control vehicle did not alter the expression levels of Mcl-1. Mel-AT cells with 5% ethanol for increasing periods. Whole cell lysates from Mel-AT cells treated were subjected to Western blot analysis. The data shown are representative of three individual experiments.(C) Mel-RM and Mel-AT cells were treated with EGb761 (400 μg/ml) or 5% ethanol for the indicated periods. Total RNA was isolated and subjected to real-time PCR analysis for Mcl-1. The relative abundance of mRNA expression treated with 5% ethanol was arbitrarily designated as 1. Columns, mean of three individual experiments; bars, SEM. * Present p<0.05 vs control.(D) Relative expression of anti-apoptosis Bcl-2 family proteins in melanoma cell lines Mel-RM and Mel-AT without treatment. Quantitative expression levels of Mcl-1, Bcl-2 and Bcl-X_L were normalized to GAPDH.(E) Relative expression of pro-apoptosis Bcl-2 family proteins in melanoma cell lines Mel-RM and Mel-AT without treatment. Quantitative expression levels of Bax, Bid, Noxa, PUMA, Bim, Bad and Bak were normalized to GAPDH.</p

Mcl-1 plays critical roles in regulating the sensitivity of melanoma cells to apoptosis induced by EGb761.

<p>(A) Knockdown of Mcl-1by siRNA decreases the levels of Mcl-1expression. Mel-RM and Mel-AT cells were transfected with scramble SiRNA or Mcl-1siRNA. Whole cell lysates were then subjected to Western blot analysis.(B) Inhibition of Mcl-1 by siRNA induces apoptosis of melanoma and sensitizes melanoma cells to EGb761-induced apoptosis. Mel-RM and Mel-AT cells were transfected with scramble or Mcl-1siRNA. 24hours later, the cells were switched into normal culture medium for a further 48 h followed by treatment with 5% ethanol or EGb761. After another 24 hours, the cells were subjected to measurement of sub-G1content by the propidiumiodide method using flow cytometry. The data shown are the mean ± SEM of three individual experiments. * Present p<0.05 vs control.(C) Knockdown Mcl-1 can affect Bax and Bak activation status in Mel-RM cells. SiRNA inhibition of Mcl-1 resulted in a marked increase in the levels of conformational changed Bax and Bak, which detected by flow cytometry. The open and filled histograms were generated from control (5% ethanol) (C) and EGb761-treated (E) cells respectively. The numbers represent MFIs. The data shown are representative of three individual experiments.(D) Expression of Mcl-1 in a panel of melanoma cell lines after treatment with EGb761 or control (5% ethanol) for 24 hours. Whole cell lysates from melanoma cells were subjected to Western blot analysis. The data shown are representative of three individual experiments.</p

EGb761 inhibits cell growth and induces apoptosis in melanoma cells in vitro.

<p>(A) Effects of EGb761 on proliferation in Mel-RM and Mel-AT cells. After EGb761 treatment at indicated concentration (100-800ug/ml) or 5% ethanol treatment as the vehicle control, Mel-RM and Mel-AT cells proliferation was assessed in a 96-well plate at 72 hours by MTT assay. The data shown are the mean ± SEM of three individual experiments. (B) Representative dot plots showing fluorescence channel analyses of melanoma cells after dual staining with Annexin V and propidium iodide. Melanocytes, Mel-RM and Mel-AT cells were treated with EGb761 at 400 μg/ml for 24h (5% ethanol treatment as the vehicle control) and then stained with FITC-conjugated Annexin V (green fluorescence, horizontal axis) and PI(red fluorescence, vertical axis), and analyzed using flow cytometry. The data shown are representative of three individual experiments. (C) EGb761 induces apoptosis of melanoma cells. Mel-RM and Mel-AT cells treated with EGb761 (100–800 μg/ml) or 5% ethanol treatment as the vehicle control for indicated intervals were subjected to measurement of apoptosis by the Annexin V/PI staining method using flow cytometry. The data shown are the mean ± SEM of three individual experiments. (D) Induction of apoptosis by EGb761 in a panel of melanoma cell lines and melanocytes. Cells treated with EGb761 (400 μg/ml) or 5% ethanol for 24h were subjected to measurement of sub-G1content by the propidiumiodide method using flow cytometry. Columns, mean of three individual experiments; Bars, SEM.</p

Apoptosis of melanoma induced by EGb761 involves activation of Bax and Bak and changes in mitochondria.

<p>(A) EGb761 induces reduction in ΔΨm. Mel-RM and Mel-AT cells treated with EGb761 (400 μg/ml) for the indicated intervals were subjected to measurement of ΔΨm by JC-1staining in flow cytometry. The number in each left bottom quadrant represents the percentage of cells with reduction in ΔΨm. The data shown are representative of three individual experiments. (B) EGb761 induces activation of Bax and Bak. Mel-RM and Mel-AT cells treated with EGb761 (400 μg/ml) for the indicated intervals were subjected to measurement of activation of Bax and Bak by flow cytometry using antibodies that specifically recognize activated Bax and Bak, respectively. The filled and open histograms were generated from control (5% ethanol treated) (C) and EGb761-treated cells (E), respectively. The numbers represent MFIs. The data shown are representative of three individual experiments. (C) EGb761 induces mitochondrial release of cytochrome c and AIF. Mitochondrial and cytosolic fractions from Mel-RM and Mel-AT cells treated with EGb761 (400 μg/ml) for 16h were subjected to Western blot analysis. COX IV or GAPDH levels were included to show relative purity of the mitochondrial or cytosolic fractions. The data shown are representative of three individual experiments.</p