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We designed a novel 6-point electrochemical impedance spectroscopy (EIS) sensor with 15 combinations of permutations for the 3-D mapping and detection of metabolically active atherosclerotic lesions. Two rows of 3 stretchable electrodes circumferentially separated by 120° were mounted on an inflatable balloon for intravascular deployment and endoluminal interrogation. The configuration and 15 permutations of 2-point EIS electrodes allowed for deep arterial penetration via alternating current (AC) to detect varying degrees of lipid burden with distinct impedance profiles (Ω). By virtue of the distinctive impedimetric signature of metabolically active atherosclerotic lesions, a detailed impedance map was acquired, with the 15 EIS permutations uncovering early stages of disease characterized by fatty streak lipid accumulation in the New Zealand White rabbit model of atherosclerosis. Both the equivalent circuit and statistical analyses corroborated the 3-D EIS permutations to detect small, angiographically invisible, lipid-rich lesions, with translational implications for early atherosclerotic disease detection and prevention of acute coronary syndromes or strokes.

Plaque rupture causes acute coronary syndromes and stroke. Intraplaque oxidized low density lipoprotein (oxLDL) is metabolically unstable and prone to induce rupture. We designed an intravascular ultrasound (IVUS)-guided electrochemical impedance spectroscopy (EIS) sensor to enhance the detection reproducibility of oxLDL-laden plaques. The flexible 2-point micro-electrode array for EIS was affixed to an inflatable balloon anchored onto a co-axial double layer catheter (outer diameter = 2 mm). The mechanically scanning-driven IVUS transducer (45 MHz) was deployed through the inner catheter (diameter = 1.3 mm) to the acoustic impedance matched-imaging window. Water filled the inner catheter to match acoustic impedance and air was pumped between the inner and outer catheters to inflate the balloon. The integrated EIS and IVUS sensor was deployed into the ex vivo aortas dissected from the fat-fed New Zealand White (NZW) rabbits (n=3 for fat-fed, n= 5 normal diet). IVUS imaging was able to guide the 2-point electrode to align with the plaque for EIS measurement upon balloon inflation. IVUS-guided EIS signal demonstrated reduced variability and increased reproducibility (p < 0.0001 for magnitude, p < 0.05 for phase at < 15 kHz) as compared to EIS sensor alone (p < 0.07 for impedance, p < 0.4 for phase at < 15 kHz). Thus, we enhanced topographic and EIS detection of oxLDL-laden plaques via a catheter-based integrated sensor design to enhance clinical assessment for unstable plaque.

Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 µm in diameter and separated by 400 µm was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Ω) and phase (ϕ) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy.

The coronavirus disease (COVID-19) pandemic fundamentally disrupted humans’ social life and behavior. Public health measures may have inadvertently impacted how people care for each other. This study investigated prosocial behavior, its association well-being, and predictors of prosocial behavior during the first COVID-19 pandemic lockdown and sought to understand whether region-specific differences exist. Participants (N = 9,496) from eight regions clustering multiple countries around the world responded to a cross-sectional online-survey investigating the psychological consequences of the first upsurge of lockdowns in spring 2020. Prosocial behavior was reported to occur frequently. Multiple regression analyses showed that prosocial behavior was associated with better well-being consistently across regions. With regard to predictors of prosocial behavior, high levels of perceived social support were most strongly associated with prosocial behavior, followed by high levels of perceived stress, positive affect and psychological flexibility. Sociodemographic and psychosocial predictors of prosocial behavior were similar across regions.

Abstract Background The Montessori Method underpinned by the principle of person-centered care has been widely adopted to design activities for people with dementia. However, the methodological quality of the existing evidence is fair. The objectives of this study are to examine the feasibility and effects of a culturally adapted group-based Montessori Method for Dementia program in Chinese community on engagement and affect in community-dwelling people with dementia. Methods This was a two-arm randomized controlled trial. People who were aged 60 years or over and with mild to moderate dementia were recruited and randomly assigned to the intervention group to receive Montessori-based activities or the comparison group to receive conventional group activities over eight weeks. The attendance rates were recorded for evaluating the feasibility. The Menorah Park Engagement Scale and the Apparent Affect Rating Scale were used to assess the engagement and affect during the activities based on observations. Generalized Estimating Equation model was used to examine the intervention effect on the outcomes across the sessions. Results A total of 108 people with dementia were recruited. The average attendance rate of the intervention group (81.5%) was higher than that of the comparison group (76.3%). There was a significant time-by-group intervention effect on constructive engagement in the first 10 minutes of the sessions (Wald χ2 = 15.21–19.93, ps = 0.006–0.033), as well as on pleasure (Wald χ2 = 25.37–25.73, ps ≤ 0.001) and interest (Wald χ2 = 19.14–21.11, ps = 0.004–0.008) in the first and the middle 10 minutes of the sessions, adjusted for cognitive functioning. Conclusions This study provide evidence that Montessori-based group activities adapted to the local cultural context could effectively engage community-dwelling Chinese older people with mild to moderate dementia in social interactions and meaningful activities and significantly increase their positive affect. Trial registration ClinicalTrials.gov, NCT04352387. Registered 20 April 2020. Retrospectively registered.

Abstract Sanwei-Tanxiang powder (SWTX), a traditional Mongolian and Tibetan medicine containing a cocktail of active molecules, relieves angina pectoris and improves recovery in patients with coronary heart disease (CHD). The pharmacological effect of SWTX on CHD was analyzed at a systemic point of view in our previous studies. The bioinformatics prediction showed that the PI3K/Akt/FoxO3a pathway was one of important pathways of SWTX on treatment of coronary heart disease. Based on it, the aim of this study was to evaluate the benefits of SWTX in acute myocardial ischemic-reperfused (MIR) rat in vivo and H9c2 cardiomyoblast cells under oxidative stress induced by H2O2 in vitro, and further investigate the involvement of PI3K/Akt/FoxO3a pathway in these processes. Ex vivo, under physiological conditions, SWTX did not show any modification in the heart rate and contraction amplitude. However, against a MIR injury, SWTX pretreatment provided significant protection, including reduced ST-segment elevation, pathological changes and myocardial infarct size in vivo, meanwhile, some monomers of SWTX showed antioxidant capacity and inhibited cardiomyocytic apoptosis in vitro. The effect was correlated with the activation of the PI3K/Akt/FoxO3a signaling pathway downstream and the regulation of downstream pro-apoptotic Bim of FoxO3a experimental verified by qRT-PCR, Western blot and immunofluorescent assay. In vitro, blocking Akt and p-FoxO3a activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of several active monomers (including quercetin, macelignan,methyleugenol and Santol) of SWTX against H2O2-induced injury. Collectively, these results suggest that SWTX decreases I/R injury, and the PI3K/Akt/FoxO3a pathway takes part in protection during this process, gallogen (G3) and quercetin (G8) of GZ, methyleugenol (R2) and macelignan (R7) of RDK, santol (T1) of TX are responsible at least in part for SWTX’s cardioprotection effect.

Abstract Background MicroRNA (miRNA) plays a vital role in the intervertebral disc (IVD) degeneration. The expression level of miR-573 was downregulated whereas Bax was upregulated notably in human degenerative nucleus pulposus cells. In this study, we aimed to investigate the role of miR-573 in human degenerative nucleus pulposus (NP) cells following hyperbaric oxygen (HBO) treatment. Methods NP cells were separated from human degenerated IVD tissues. The control cells were maintained in 5% CO2/95% air and the hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The mRNA and protein levels of Bax were measured. The proliferation of NPCs was detected using MTT assay. The protein expression levels of Bax, cleaved caspase 9, cleaved caspase 3, pro-caspase 9, and pro-caspase 3 were examined. Results Bioinformatics analysis indicated that the 3′ untranslated region (UTR) of the Bax mRNA contained the “seed-matched-sequence” for hsa-miR-573, which was validated via reporter assays. MiR-573 was induced by HBO and simultaneous suppression of Bax was observed in NP cells. Knockdown of miR-573 resulted in upregulation of Bax expression in HBO-treated cells. In addition, overexpression of miR-573 by HBO increased cell proliferation and coupled with inhibition of cell apoptosis. The cleavage of pro-caspase 9 and pro-caspase 3 was suppressed while the levels of cleaved caspase 9 and caspase 3 were decreased in HBO-treated cells. Transfection with anti-miR-573 partly suppressed the effects of HBO. Conclusion Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative NP cells following HBO treatment.

E7050 is a potent inhibitor of c-Met receptor tyrosine kinase and has potential for cancer therapy. However, the underlying molecular mechanism involved in the anti-cancer property of E7050 has not been fully elucidated. The main objective of this study was to investigate the anti-tumor activity of E7050 in multidrug-resistant human uterine sarcoma MES-SA/Dx5 cells in vitro and in vivo, and to define its mechanisms. Our results revealed that E7050 reduced cell viability of MES-SA/Dx5 cells, which was associated with the induction of apoptosis and S phase cell cycle arrest. Additionally, E7050 treatment significantly upregulated the expression of Bax, cleaved PARP, cleaved caspase-3, p21, p53 and cyclin D1, while it downregulated the expression of survivin and cyclin A. On the other hand, the mechanistic study demonstrated that E7050 inhibited the phosphorylation of c-Met, Src, Akt and p38 in HGF-stimulated MES-SA/Dx5 cells. Further in vivo experiments showed that treatment of athymic nude mice carrying MES-SA/Dx5 xenograft tumors with E7050 remarkably suppressed tumor growth. E7050 treatment also decreased the expression of Ki-67 and p-Met, and increased the expression of cleaved caspase-3 in MES-SA/Dx5 tumor sections. Therefore, E7050 is a promising drug that can be developed for the treatment of multidrug-resistant uterine sarcoma.

Introduction: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. Methods: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. Results: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35–1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12–0.85; p = 0.013). Conclusion: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs. [ABSTRACT FROM AUTHOR]

The northeastern Sichuan area in the northern Yangtze margin has unique Ediacaran geological records, especially the Doushantuo Formation (DST), and become a hot research area in recent years. However, the Cryogenian-Ediacaran (C-E) boundary has not been precisely identified, which restricts the in-depth study of geological information during this crucial transitional period and is unfavorable for a systematic and complete understanding of the Yangtze Block and even the global paleogeographic pattern. This study conducted stratigraphy, sedimentology, and chronostratigraphy to establish the stratigraphic framework and sedimentary evolution of the C-E transition strata in northeastern Sichuan. The results showed that the Ediacaran sediments, without the cap dolomite, unconformably overlaid the Cryogenian sediments in the studied area. The Member II of the DST, characterized by 50e160 m of red-green sandstone (approximately equivalent to the original Chengkou "Guanyinya Formation"), directly overlaid the Cryogenian sediments and displayed a 623 ± 2.3 Ma maximum depositional age from the detrital zircon UePb dating. Regional stratigraphic correlations indicate that the C-E transition strata in northeastern Sichuan had a consistent lithological association and sedimentary sequence characteristics but differed from the Three Gorges. Typically, the upper Nantuo massive glacial diamictites transition to the icebergs rafted lonestone-bearing mudstones at the top, then change upward to DST barrier coast sandstones. The proposed DST of the northeastern Sichuan Basin was divided into three lithostratigraphic members without the regional Member I cap dolomite: (i) Member II purple-red, gray-green sandstone strata, (ii) Member III black mudstone strata, and (iii) Member IV P-Mn bearing strata. During the C-E transition, the study area experienced (i) the global deglaciation stage in the terminal Marinoan glaciation and (ii) the filling-leveling up stage with clastic rocks in the early Ediacaran. Overall, the early Ediacaran of northeastern Sichuan succeeded the paleogeographic features of the late Cryogenian. [ABSTRACT FROM AUTHOR]

Objective: Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease‐modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD. Methods: The neuroprotective effect of CFE in H2O2‐ or 6‐OHDA‐induced PC‐12 cells and α‐synuclein‐overexpressing PC‐12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α‐synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α‐synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging‐related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria. Results: In cellular models of PD, CFE significantly attenuated H2O2‐ or 6‐OHDA‐induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α‐synuclein in wide type (WT)‐, A53T‐, A30P‐, or E46K‐α‐synuclein‐overexpressing PC‐12 cells. Our further findings reveal that CFE administration reduced α‐synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6‐OHDA‐induced degeneration in BZ555 worms, extended lifespan, delayed aging‐related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo. Conclusion: Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD. [ABSTRACT FROM AUTHOR]

In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer. The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55–75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov , NCT02611570 , and is ongoing. Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis. TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer. Ministry of Health and Welfare of Taiwan. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has become a global pandemic, which is induced by infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with systemic lupus erythematosus (SLE) are susceptible to infections due to the chronic use of immunosuppressive drugs and the autoimmune disorders. Now we report a case of SLE infected with SARS-CoV-2, influenza A virus and Mycoplasma pneumoniae concurrently. The patient used hydroxychloroquine and prednisone chronically to control the SLE. After infection of SARS-CoV-2, she was given higher dose of prednisone than before and the same dosage of hydroxychloroquine. Besides, some empirical treatments such as antiviral, antibiotic and immunity regulating therapies were also given. The patient finally recovered from COVID-19. This case indicated that hydroxychloroquine may not be able to fully protect SLE patient form SARS-CoV-2. Intravenous immunoglobulin therapies and increased dose of corticosteroids might be adoptable for patient with both COVID-19 and SLE. Physicians should consider SARS-CoV-2 virus test when SLE patient presented with suspected infection or SLE flare under the epidemic of COVID-19.

Hepatitis B virus infection is not only a huge burden in the field of social health but also a major public health problem that affects the lives and health of the people. Simple, rapid, feasible detection of HBV is critical for its prevention and spread, especially in the developing countries with low-resource laboratories. To this end, we combined multienzyme isothermal rapid amplification (MIRA) and lateral flow dipstick (LFD) strip to detect HBV. A pair of primers targeting the conserved region of HBV genome was designed and used in MIRA-LFD assay. Our results found that the entire amplification of MIRA-LFD only takes 10 min at 37°C and the dilution of the amplification products was added in the LFD strip and observed by the naked eye after 10 min. The detection sensitivity of this method can reach 10 pg. The 45 clinical samples were detected by MIRA-LFD and real-time PCR. The accuracy rate of MIRA-LFD was 100%. Therefore, these characteristics of our newly developed MIRA-LFD assay make it particularly useful and suitable for detecting HBV in the resource-limited condition.