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Bisphenol A (BPA) is an estrogen-like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE-19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE-19 cells. After BPA treatment, the expression of Bcl-XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase-9 to promote downstream caspase-3 leading to cytotoxicity. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) pathway play a major role in age-related macular degeneration. Our results showed that expression of HO-1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP-activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA-induced ROS generation and cytotoxicity were reduced by N-acetyl-l-cysteine. Taken together, these results suggest that BPA induced ARPE-19 cells via oxidative stress, which was associated with down regulated Nrf2/HO-1 pathway, and the mitochondria dependent apoptotic signaling pathway.

1-Nitropyrene (1-NP), one of the most abundant nitropolycyclic aromatic hydrocarbons (nitro-PAHs), is generated from the incomplete combustion of carbonaceous organic compounds. 1-NP is a specific marker of diesel exhaust and is an environmental pollutant and a probable carcinogen. Macrophages participate in immune defense against the invasive pathogens in heart, lung, and kidney infection diseases. However, no evidence has indicated that 1-NP induces apoptosis in macrophages. In the present study, 1-NP was found to induce concentration-dependent changes in various cellular functions of RAW264.7 macrophages including cell viability reduction; apoptosis generation; mitochondrial dysfunction; apoptosis-inducing factor (AIF) nuclear translocation; intracellular ROS generation; activation of the AMPK/Nrf-2/HO-1 pathway; changes in the expression of BCL-2 family proteins; and depletion of antioxidative enzymes (AOE), such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) These results indicate that 1-NP induced apoptosis in macrophages through AIF nuclear translocation and ROS generation due to mitochondrial dysfunction and to the depletion of AOE from the activation of the AMPK/Nrf-2/HO-1 pathway.

Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA-induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase-3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.

Introduction Atrial fibrillation (AF) was a significant independent risk factor for 1-year mortality of first acute ischemic stroke. The CHA2DS2-VASc scores were initially developed to assess the risk of stroke or systemic embolism in patients with AF. Recently, this scoring system have been demonstrated to have clinical value for predicting the severity of infarction and long-term clinical outcomes in acute ischemic stroke but the evidence is not strong enough due to limited numbers and single center data. Purpose This large-scale prospective cohort study aimed to investigate the independent predictive value of CHA2DS2-VASc scores and AF in such patients. Materials and methods We included patients from Taiwan Stroke Registry (TSR) with ischemic stroke within 2006 to 2016 as the present study population. Patients were mainly divided in atrial fibrillation (AF) group and non-AF group. We future classified patient by CHA2DS2-VASc (congestive heart failure, hypertension, age≥75 years, diabetes, previous stroke, vascular disease, age 65–74 years, sex category) score 0–1 and ≥2. The primary outcome was major adverse cardiovascular events (MACE), which include re-stroke, myocardial infarction and cardiovascular death, occurred within 1 year after the onset of stroke. The secondary outcome was the all-cause mortality. Results We defined 2972 patients with MACE and 61,937 patients without MACE. With adjusting with the confounding of CHA2DS2-VASc scores, The AF group was associated with increased MACE (OR=1.15; 95% CI=1.00, 1.33), myocardial infarction (adjusted OR=3.89; 95% CI=1.81, 8.34), CV death (OR=5.73; 95% CI=3.77, 8.69) and all-cause mortality (OR=1.50; 95% CI=1.37, 1.65) but not in re-stroke (adjusted OR=1.02; 95% CI=0.88, 1.18). After controlling for AF, patients with CHA2DS2-VASc scores ≥2 had significantly higher odds of MACE (OR=1.28; 95% CI=1.16, 1.41), re-stroke (OR=1.27; 95% CI=1.16, 1.40) and all-cause mortality (OR=2.26; 95% CI=2.06, 2.48) than that of patients with CHA2DS2-VASc scores 0–1. The survival curve revealed both AF and CHA2DS2-VASc scores are independent risk factors of 1 year MACE and mortality. By investigating the individual risk factor of CHA2DS2-VASc score, diabetes, hypertension and age over 65 years old increase the risk of MACE significantly. Conclusions CHA2DS2-VASc scores appear to have potent independent value as AF for predicting 1 year MACE and all-cause mortality in patients of acute ischemic stroke. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Bisphenol A (BPA) is an estrogen-like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE-19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE-19 cells. After BPA treatment, the expression of Bcl-XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase-9 to promote downstream caspase-3 leading to cytotoxicity. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) pathway play a major role in age-related macular degeneration. Our results showed that expression of HO-1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP-activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA-induced ROS generation and cytotoxicity were reduced by N-acetyl-l-cysteine. Taken together, these results suggest that BPA induced ARPE-19 cells via oxidative stress, which was associated with down regulated Nrf2/HO-1 pathway, and the mitochondria dependent apoptotic signaling pathway.

Acute lung injury (ALI) is a life-threatening disease that is characterised by the rapid onset of inflammatory responses. Lipopolysaccharide (LPS) is an endotoxin that plays an important role in triggering ALI via pneumonia and sepsis. However, no effective therapeutic strategies are currently available to treat ALI. Nerolidol is an aliphatic sesquiterpene alcohol that is found in the essential oils of many flowers as well as floral plants. It has been shown to exhibit anti-inflammatory, antioxidant, and anticancer properties. Herein, we show that nerolidol pretreatment counteracted the histopathological hallmarks in LPS-induced ALI mice. Indeed, nerolidol pretreatment inhibited LPS-induced alveolar-capillary barrier disruption, lung edema, and lipid peroxidation. Moreover, nerolidol pretreatment prevented the LPS from decreasing the enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase. Importantly, nerolidol treatment enhanced phosphorylation of AMP-activated protein kinase (AMPK) and expression of nuclear factor erythroid-derived 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Taken together, our study reveals the novel protective effects of nerolidol in LPS-induced ALI via the induction of antioxidant responses and activation of the AMPK/Nrf-2/HO-1 signalling pathway.

Deep vein thrombosis (DVT) of lower limbs can easily arise from prolonged sitting or standing. Elders and pregnant women are most likely to have this disease. When the embolus of DVT comes to pass the lung, it will become a life-threatening disease. Thus, for DVT disease, early detection and the early treatment are needed. The goal of this study was to develop an examination system to be used at non-medical places to detect the DVT of lower limbs with light reflection rheography (LRR). Consisting of a wearable device and a mobile application (APP), the system is operated in a wireless manner to control the actions of sensors and display and store the LRR signals on the APP. Then, the recorded LRR signals are processed to find the parameters of DVT examination. Twenty subjects were recruited to perform experiments. The veins of lower limbs were occluded by pressuring the cuff up to 100 mmHg and 150 mmHg to simulate the slight and serious DVT scenarios, respectively. Six characteristic parameters were defined to classify whether there was positive or negative DVT using the receiver operating characteristic curves, including the slopes of emptying and refilling curves in the LRR signal, and the changes of venous pump volume. Under the slight DVT scenario (0 mmHg vs. 100 mmHg), the first three parameters, m10, m40, and m50, had accuracies of 72%, 69%, and 69%, respectively. Under the serious DVT scenario (0 mmHg vs. 150 mmHg), m10, m40, and m50 achieved accuracies of 73%, 76%, and 73%, respectively. The experimental results show that this proposed examination system may be practical as an auxiliary tool to screen DVT in homecare settings.

Despite minoxidil and finasteride already being approved by the Food and Drug Administration (FDA) for the treatment of hair loss, it is important to identify new and innovative treatments for hair loss, such as looking for a solution in Chinese herbal medicine. One such treatment to consider is BeauTop (BT), whose primary ingredients include Panax japonicus (T.Nees), C.A. Mey. (Araliaceae), Astragalus membranaceus (Fisch) Bunge (Fabaceae), Angelica sinensis (Oliv.) Diels (Apiaceae), Ligustrum lucidum W.T. Aiton (Oleaceae), Rehmannia glutinosa (Gaertn.) DC. (Plantaginaceae), and Eclipta prostrata (L.) L. (Compositae). The aim of this study was to evaluate whether BT can promote hair growth in C57BL/6 mice and to investigate hair coverage, the expression of vascular endothelial growth factor (VEFG), and the numbers of hair follicles in growth phase after oral administration. A total of 12 C57BL/6 mice were divided into two groups: control group and treatment group BT. BT was administered orally as an extract at a volume of 0.6 g/kg. The control group was treated with distilled water. Each group was treated once a day for 12 consecutive days. To observe the expression of VEGF distribution, the number of hair follicles and the hair coverage were examined on days 4, 8, and 12. By comparing the treatment group and control group, we found that VEGF in the BT group on day 8 presented with a higher area percentage than the control group (pvalue = 0.003). Hair follicle counting results showed that the BT group was significantly higher than the control group on day 8 (pvalue = 0.031). Furthermore, hair coverage was shown to be significantly increased in the treatment group BT on day 8 (pvalue = 0.013). Taken together, these results suggest that Chinese medicine (BT) possesses the potential effect of promoting hair growth through VEGF expression. VEGF is considered the most important mediator for the process of angiogenesis involved in hair growth development.

Recent clinical trials showed that short aspirin duration (1 or 3 months) in dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy reduced the risk of bleeding and did not increase the ischemic risk compared to 12-month DAPT in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). However, it is unclear about the optimal duration of aspirin in P2Y12 inhibitor monotherapy. The purpose of this study was to evaluate the influence of aspirin treatment duration on clinical outcomes in a cohort of ACS patients with early aspirin interruption and received P2Y12 inhibitor monotherapy. From January 1, 2014 to December 31, 2018, we included 498 ACS patients (age 70.18 ± 12.84 years, 71.3% men) with aspirin stopped for various reasons before 6 months after PCI and received P2Y12 inhibitor monotherapy. The clinical outcomes between those with aspirin treatment ≤ 1 month and > 1 month were compared in 12-month follow up after PCI. Inverse probability of treatment weighting was used to balance the covariates between groups. The mean duration of aspirin treatment was 7.52 ± 8.10 days vs. 98.05 ± 56.70 days in the 2 groups (p 1 month. Our results indicated that ≤ 1-month aspirin may be enough in P2Y12 inhibitor monotherapy strategy for ACS patients undergoing PCI.

Currently, in terms of reducing the infection risk of the COVID-19 virus spreading all over the world, the development of touchless blood pressure (BP) measurement has potential benefits. The pulse transit time (PTT) has a high relation with BP, which can be measured by electrocardiogram (ECG) and photoplethysmogram (PPG). The ballistocardiogram (BCG) reflects the mechanical vibration (or displacement) caused by the heart contraction/relaxation (or heart beating), which can be measured from multiple degrees of the body. The goal of this study is to develop a cuffless and touchless BP-measurement method based on a commercial weight scale combined with a PPG sensor when measuring body weight. The proposed method was that the PTTBCG-PPGT was extracted from the BCG signal measured by a weight scale, and the PPG signal was measured from the PPG probe placed at the toe. Four PTT models were used to estimate BP. The reference method was the PTTECG-PPGF extracted from the ECG signal and PPG signal measured from the PPG probe placed at the finger. The standard BP was measured by an electronic blood pressure monitor. Twenty subjects were recruited in this study. By the proposed method, the root-mean-square error (ERMS) of estimated systolic blood pressure (SBP) and diastolic blood pressure (DBP) are 6.7 ± 1.60 mmHg and 4.8 ± 1.47 mmHg, respectively. The correlation coefficients, r2, of the proposed model for the SBP and DBP are 0.606 ± 0.142 and 0.284 ± 0.166, respectively. The results show that the proposed method can serve for cuffless and touchless BP measurement.

Objectives: Currently, diabetes mellitus (DM) and chronic obstructive pulmonary disease (COPD) have proven to be risk factors for each other. This study aimed to determine the risk relationship between COPD and five common oral medications for DM among patients with DM. Methods: This population-based cohort study was conducted from 2008 to 2013. Patient data were retrieved from the Longitudinal Health Insurance Database (LHID) of the National Health Insurance Research Database (NHIRD). After pairing by gender, age, and index date, time-to-event analysis and multiple regression analysis were performed to determine the factors associated with COPD in patients taking oral medication for DM, including age, gender, income, and comorbidities. We identified 1,028 patients who took oral medication for DM and 1,028 controls who did not take oral medication for DM. Results: We observed that the use of α-glucosidase inhibitors was associated with a higher risk of COPD (hazard ratio [HR]: 1.964, 95% confidence interval [CI]: 1.207-2.380). Furthermore, compared with the control group, α-glucosidase inhibitor users had a higher risk of COPD (HR: 2.295, 95% CI: 1.304-4.038), and no significant difference was observed in other oral medications for DM. Conclusions: Based on present results, we could suggest that patients with DM who used α-glucosidase inhibitors are probably a higher risk of COPD. We recommend that in the future, treatment with α-glucosidase inhibitors upregulate the occurrence of COPD might through gastrointestinal side effects and malnutrition.

Background P2Y12 inhibitor monotherapy with either clopidogrel or ticagrelor becomes an alternative antiplatelet strategy in patients (pts) undergoing percutaneous coronary intervention (PCI). The purpose of this study was to compare the efficacy and safety of clopidogrel vs. ticagrelor monotherapy in pts with acute coronary syndrome (ACS) undergoing PCI who cannot tolerate aspirin. Methods and results From January 1, 2014 to December 31, 2018, a total of 610 ACS pts (mean age 70.4±13.1 years, 72.1% men, 28.5% STEMI) that aspirin was stopped prematurely for various reasons and received either clopidogrel (n=369) or ticagrelor (n=241) monotherapy were included from 8 major hospitals in Taiwan. The duration (median and the 25th and 75th percentile) of aspirin treatment was 9 (1.39–37.00) days in the clopidogrel group and 10 (1.00–55.00) days in the ticagrelor group (p=0.514). Gastrointestinal bleeding (36.9%) was the most common reason to stop aspirin in both groups. The primary endpoint is the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months after discharge. The safety endpoint was the major bleeding defined as BARC 3 or 5 bleedings. The covariates were balanced between groups after using inverse probability of treatment weighting. Overall, 84 patients developed events of primary endpoint, with 57 (15.4%) in the clopidogrel group and 27 (11.2%) in the ticagrelor group. After multivariate adjustment in the Cox proportional-hazards models, ticagrelor was associated with a lower risk of primary endpoint compared with clopidogrel (adjusted hazard ratio [aHR] 0.67, 95% CI 0.49–0.93). Among the primary endpoint, ticagrelor significantly reduced the risk of recurrent ACS or unplanned revascularization (aHR 0.46, 95% CI 0.28–0.75). There was no significant difference of all-cause mortality between the 2 groups (aHR 0.92, 95% CI 0.52–1.61). The risk of BARC 3 or 5 bleeding was also similar (aHR 0.71, 95% CI 0.35–1.45). Conclusions Among ACS patients undergoing PCI who cannot tolerate aspirin, ticagrelor monotherapy was associated with a significantly lower risk of a composite of cardiovascular events compared to clopidogrel monotherapy. The major bleeding risk was similar between groups. Funding Acknowledgement Type of funding source: None

Genotoxic stress from environmental pollutants plays a critical role in cytotoxicity. The most abundant nitro-polycyclic aromatic hydrocarbon in environmental pollutants, 1-nitropyrene (1-NP), is generated during fossil fuel, diesel, and biomass combustion under sunlight. Macrophages, the key regulators of the innate immune system, provide the first line of defense against pathogens. The toxic effects of 1-NP on macrophages remain unclear. Through a lactate dehydrogenase assay, we measured the cytotoxicity induced by 1-NP. Our results revealed that 1-NP induced genotoxicity also named DNA damage, including micronucleus formation and DNA strand breaks, in a concentration-dependent manner. Furthermore, 1-NP induced p53 phosphorylation and nuclear accumulation; mitochondrial cytochrome c release; caspase-3 and -9 activation and cleavage; and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage in a concentration-dependent manner. Pretreatment with the PARP inhibitor, 3-aminobenzamide, significantly reduced cytotoxicity, genotoxicity, and PARP-1 cleavage induced by 1-NP. Pretreatment with the caspase-3 inhibitor, z-DEVD-fmk, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, and caspase 3 activation induced by 1-NP. Pretreatment with the p53 inhibitor, pifithrin-α, significantly reduced cytotoxicity, genotoxicity, PARP-1 cleavage, caspase 3 activation, and p53 phosphorylation induced by 1-NP. We propose that cytotoxicity and genotoxicity induced by 1-NP by PARP-1 cleavage via caspase-3 and -9 activation through cytochrome c release from mitochondria and its upstream p53-dependent pathway in macrophages.

One of the major missions of the Taiwan Society of Cardiology is to publish practice guidelines that are suitable for local use in Taiwan. The ultimate purpose is to continuously improve cardiovascular health care from the implementation of the recommendations in the guidelines. Despite recent improvement of medical care, patients with ST-segment elevation myocardial infarction (STEMI) still carry a high morbidity and mortality. There have been many changes in the concepts of STEMI diagnosis and treatment in recent years. The 2020 focused update of the 2012 guidelines of the Taiwan Society of Cardiology for the management of STEMI is an amendment of the 2012 guidelines based on the newest published scientific data. The recommendations in this focused update provide the diagnosis and treatment strategy for STEMI that should be generally implemented in Taiwan. Nevertheless, guidelines never completely replace clinical judgment and medical decision still should be determined individually.

Background: P2Y12 inhibitor monotherapy is an alternative antiplatelet strategy in patients undergoing percutaneous coronary intervention (PCI). However, the ideal P2Y12 inhibitor for monotherapy is unclear. Methods and Results: We performed a multicenter, retrospective, observational study to compare the efficacy and safety of monotherapy with clopidogrel versus ticagrelor in patients with acute coronary syndrome (ACS) undergoing PCI. From 1 January 2014 to 31 December 2018, 610 patients with ACS who received P2Y12 monotherapy with either clopidogrel (n = 369) or ticagrelor (n = 241) after aspirin was discontinued prematurely were included. Inverse probability of treatment weighting was used to balance covariates between the groups. The primary endpoint was the composite of all-cause mortality, recurrent ACS or unplanned revascularization, and stroke within 12 months after discharge. Overall, 84 patients reached the primary endpoint, with 57 (15.5%) in the clopidogrel group and 27 (11.2%) in the ticagrelor group. Multivariate adjustment in Cox proportional-hazards models revealed a lower risk of the primary endpoint with ticagrelor than with clopidogrel (adjusted hazard ratio (aHR): 0.67, 95% confidence interval (CI): 0.49&ndash, 0.93). Ticagrelor significantly reduced the risk of recurrent ACS or unplanned revascularization (aHR: 0.46, 95% CI: 0.28&ndash, 0.75). No significant difference in all-cause mortality and major bleeding events was observed between the 2 groups. Conclusions: Among patients with ACS undergoing PCI who cannot complete course of dual antiplatelet therapy, a significantly lower risk of cardiovascular events was associated with ticagrelor monotherapy than with clopidogrel monotherapy. The major bleeding risk was similar in both the groups.

Photoplethysmography (PPG) has been extensively employed to acquire some physiological parameters such as heart rate, oxygen saturation, and blood pressure. However, PPG signals are frequently corrupted by motion artifacts and baseline wandering, especially for the reflective PPG sensor. Several different algorithms have been studied for determining the signal quality of PPG by the characteristic parameters of its waveform and the rule-based methods. The levels of signal quality usually were defined by the manual operations. Thus, whether the good PPG waveforms are enough to increase the accuracy of the measurement is still a subjective issue. The aim of this study is to use a fuzzy neural network to determine the signal quality indexes (SQI) of PPG pulses measured by the impedance cardiography. To test the algorithm performance, the beat-to-beat stroke volumes (SV) were measured with our device and the medis&reg, CS 2000, synchronously. A total of 1466 pulses from 10 subjects were used to validate our algorithm in which the SQIs of 1007 pulses were high, those of 71 pulses were in the middle, and those of 388 pulses were low. The total error of SV measurement was &minus, 18 &plusmn, 22.0 mL. The performances of the classification were that the sensitivity and specificity for the 1007 pulses with the high SQIs were 0.81 and 0.90, and the error of SV measurement was 6.4 &plusmn, 12.8 mL. The sensitivity and specificity for the 388 pulses with the low SQIs were 0.84 and 0.93, while the error of SV measurement was 30.4 &plusmn, 3.6 mL. The results show that the proposed algorithm could be helpful in choosing good-quality PPG pulses to increase the accuracy of SV measurement in the impedance plethysmography.

Artificial intelligence has been widely used in the biomedical engineering field, which can assist the clinicians in disease diagnoses, help the engineers in physiological signal processing, or serve the people with chronic diseases in the homecare management. Blood clots in the deep veins of human body is called the deep vein thromboses (DVT). If the embolus passes through the lung, patient will have a life-threatening risk. Therefore, how to use the artificial intelligence to serve daily monitoring of the DVT condition is a valuable exploration. The light reflection rheography (LRR) has been used to detect the DVT of low limbs. In the previous study, the wearable device using LRR technique has been developed. But, this examination system could not be used by non-physician because the signal-quality evaluation of LRR and the classification of positive or negative DVT using the LRR signal all need the manual process. The goal of this study is to use a two-dimension convolutional neural network (2D CNN) to evaluate the qualities of LRR signals and classify the positive or negative DVT from the LRR signal with high reliability. The LRR signal and the smoothed signal were combined together to form a 450x450 image as the input pattern. In this study, twenty subjects were recruited to perform four-time experiments. A cuff pressured to 100 mmHg and 150 mmHg occluded the veins of low limbs to simulate the slight and serious DVT scenarios, and which was placed at the top and bottom of the knee of left leg to simulate the distal and proximal embolization. In the signal-quality evaluation, there were 700 samples including 476 high qualities and 224 low qualities, which were marked by the experts according to the vein emptying phenomenon. In the DVT classification, there were 476 samples including 167 negative samples, 158 slight positive samples, and 151 serious positive samples. A 19-layer CNN model proposed by Visual Geometry Group (VGG-19) was used in the two experiments. We performed the inter-group and intra-group analysis. Both results were better than the previous study. The accuracies of signal-quality evaluation and DVT classification were 0.92 and 0.75, respectively. Thus, the proposed method could support people with the high risk for DVT examination at non-medical settings.

Cigarette smoking is a well-established risk factor for various diseases, such as cardiovascular diseases, neurodegeneration, and cancer. Cadmium nitrate (Cd(NO3)2) is one of the major products from the cigarette smoke. Up to now, no supporting evidence on Cd(NO3)2-induced apoptosis and its related working mechanism in neurons has been found. In present study, the mode of cell death, caspase activities, reactive oxygen species (ROS) generation, and mitochondrial dysfunction in N2a cells, which are neuron-like cells, were assessed by Annexin V-FITC and PI assays, caspase fluorometric assay, DCFH-DA fluorescence assay, and JC-1 fluorescence assay respectively. The results showed that not only Cd(NO3)2 induced apoptosis and necrosis but also the activities of caspase-3 and -9 expressed in a concentration-dependent manner. In addition, Cd(NO3)2 also induced both mitochondrial dysfunction and ROS generation in a concentration-dependent manner. All these indicated that in N2a cells parallel trends could be observed in apoptosis, caspase-3 and -9 activities, mitochondrial dysfunction, and ROS generation when induced by Cd(NO3)2. Furthermore, Cd(NO3)2-induced apoptosis, caspases activities, mitochondrial dysfunction, and ROS generation were reduced by N-acetyl-l-cysteine (NAC). These results indicated that Cd(NO3)2-induced neuronal apoptosis was reduced by NAC via intrinsic apoptotic caspase cascade activities and their up-stream factors, including mitochondrial dysfunction and ROS generation.

Safrole is a natural compound categorized as a group 2B carcinogen extracted from betel quid chewing, which is a common practice of psychoactive habits integrated into social and cultural ceremonies among serveral million people, especially in Southern or Southeastern Asia. Safrole is one of the major risk compunds for development of oral squamous cell carcinoma and hepatocellular carcinoma via DNA adduction. In innate immunity, macrophages are the predominant cells for non-specific first line defense against pathogens in oral tissue. Up to now, there is no evidence to implicate the potential toxicological effect of safrole on macrophages. In this study, we found safrole induced the generation of reactive oxygen species (ROS) and myeloperoxidase (MPO) in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, cytotoxicity, DNA damage, and apoptosis were caused by safrole in a concentration-dependent manner. While the activation of antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was reduced, the phosphorylation of Akt was induced by safrole in a concentration-dependent manner. These results indicated that the induction of cytotoxicity, DNA damage, and apoptosis in macrophages by safrole was through generation of ROS and inhibition of antioxidative enzymes possibly via Akt phosphorylation.

Acute lung injury (ALI) is a clinical syndrome with high morbidity and mortality rates mainly caused by Gram-negative bacteria. Nevertheless, an effective treatment strategy for ALI is yet to be developed. Zerumbone, a sesquiterpene isolated from Zingiber zerumbet Smith, possesses several advantageous bioeffects such as antioxidation, anti-inflammation, and antiulcer. Pretreatment of zerumbone inhibited lipopolysaccharide (LPS)-induced arterial blood gas exchange, neutrophils infiltration, and increased pulmonary vascular permeability. LPS-induced expression of intercellular adhesion molecule-1 (ICAM-1) was inhibited by zerumbone at a lower concentration than that of vascular cell adhesion molecule-1 (VCAM-1). In addition, proinflammatory cytokines, such as interleukin (IL)-1β and macrophage inflammatory protein (MIP)-2 were suppressed by zerumbone. The phosphorylation of nuclear factor (NF)-κB, a proinflammatory transcription factor, and degradation of inhibitor of κB (IκB), an inhibitor of NF-κB, were also reduced by zerumbone. Furthermore, we found the inhibitory concentration of zerumbone on phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) was lower than that of extracellular signal-regulated kinase (ERK). In conclusion, zerumbone could be a potential protective agent for ALI, possibly via expression of ICAM-1, IL-1β, and MIP-2. The protective mechanism of zerumbone was by reversing the activation of p38 MAPK/JNK-IκB/NF-κB pathway.