The use of online MBSR audio in medical staff during the COVID-19 in China.

OBJECTIVE: This study aims to survey medical staff's acceptance of online Mindfulness-Based Stress Reduction (MBSR) during the Novel Coronavirus Pneumonia (NCP), and to know some information of physical and emotional response of those medical staff who worked at the forefront of COVID-19, through the playback amount of the online MBSR training. MATERIALS AND METHODS: Considering the working environment of medical staff in forefront of NCP, we designed and recorded MBSR audio album including 13 sessions, covering 24 hours of a day, then sent the album to medical staff who had been working in Wuhan, Hubei province, China. We collected the playback amount in each session on February 10th and February 24th, which were one week and three weeks after the album was finished. RESULTS: On February 10th and February 24th, there were separately 5778 and 10640 times of broadcasting. The highest broadcasting frequency session was at 5:00 am, followed by 7:00 am. The least broadcasting frequency sessions were 17:00 pm and 19:00 pm. The broadcasting amount in the 6 periods of the night (from 21:00 pm to 7:00 am) was significantly higher than those in the daytime (from 9:00 am to 19:00 pm), with a statistical difference. The tendency of the amount of playback was consistent, which was not affected by the specific content of the mindfulness exercises. CONCLUSIONS: Online MBSR exercises were well accepted by medical staff in the COVID-19. It may help them relax and reduce the risk of stress reactions. During the NCP, medical staff may have different degrees of sleep and emotional problems, which need to be paid more attention to.

LncRNATCF7 up-regulates DNMT1 mediated by HPV-18 E6 and regulates biological behavior of cervical cancer cells by inhibiting miR-155.

OBJECTIVE: This work aimed to study the mechanism of lncRNATCF7 upregulating DNMT1 mediated by HPV-18 E6 and regulating the biological behavior of cervical cancer cells by inhibiting miR-155. PATIENTS AND METHODS: HPV-16 E6 enhanced DNMT1 expression in cervical cancer cells, which was detected by Western blotting. The expression of miR-155 in cervical cancer was detected by qPCR, the interaction between TCF-7 and miR-155 by Dual-luciferase reporter gene. The changes in invasion ability of cervical cancer cells and the effect of miR-155 on the invasion ability of cervical cancer cells after inhibiting TCF-7 were detected by the transwell invasion assay, while changes in migration ability of cervical cancer cells and the effect of miR-155 on migration ability of cervical cancer cells after inhibiting TCF-7 were observed by the scratch assay. The effect of inhibiting TCF-7 on the tumor size and volume of cervical cancer was detected by the subcutaneous tumor formation in nude mice. RESULTS: E6 expression was significantly inhibited by E6 siRNA. The knockdown of endogenous HPV-16 E6 markedly inhibited the expression of DNMT1; TCF-7 specifically bound to the 3' UTR of miR-155; inhibition of TCF-7 can inhibit invasion and migration of cervical cancer cells; enhanced miR-155 after the inhibition of TCF-7 can promote the invasion and migration of cervical cancer cells; compared with NC group, the tumor volume and weight of TCF-7-siRNA group tumor-bearing was significantly reduced. CONCLUSIONS: TCF-7 plays an important role in the development of cervical cancer. TCF-7 can target miR-155 to regulate the invasion and migration of cervical cancer cells.

Increased EWSAT1 expression promotes cell proliferation, invasion and epithelial-mesenchymal transition in colorectal cancer.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have recently been identified as crucial regulators in colorectal cancer (CRC) progression. The aim of the study is to investigate the clinical role and biological effects of long non-coding RNA EWSAT1 in CRC. PATIENTS AND METHODS: The expression of lncRNA EWSAT1 was detected in 106 cases of fresh CRC tissues and matched adjacent normal tissues by qRT-PCR analyses. The Kaplan-Meier analysis and log-rank test were used to assess the association between lncRNA EWSAT1 expression and overall survival (OS) rate of CRC patients. Cell proliferation and invasion capacity were evaluated by CCK8 assay, colony formation, and transwell invasion assays. The protein expression was detected using western blot analysis. RESULTS: LncRNA EWSAT1 expression was abnormally higher in CRC tissues compared to matched adjacent normal tissues. Higher lncRNA EWSAT1 expression significantly associated with depth of invasion, lymph node metastasis, and advanced tumor-node-metastasis (TNM) stage in CRC patients. Patients with higher EWSAT1 expression exhibited shorter OS compared with patients with lower EWSAT1 expression. Furthermore, lncRNA EWSAT1 knockdown significantly suppressed cell proliferation and invasion in CRC. In addition, lncRNA EWSAT1 knockdown suppressed cell epithelial-mesenchymal transition (EMT) through reducing Snail1, Snail2, and N-cadherin expression, but increasing E-cadherin expression in CRC cells. CONCLUSIONS: Downregulation of lncRNA EWSAT1 suppressed cell proliferation and invasion of CRC, which indicated that EWSAT1 may be a potential target of CRC treatment.

Propranolol inhibits the proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms

The aim of this study was to investigate the mechanism of propranolol on the regression of hemangiomas. Propranolol-treated hemangioma tissues were collected and the expression of hypoxia inducible factor-1α (HIF-1α) was examined. We also established HIF-1α overexpression and knockdown hemangioma cells, and determined the effects of HIF-1α on the hemangioma cells proliferation, apoptosis, migration and tube formation. Significantly increased HIF-1α level was found in the hemangioma tissues compared to that in normal vascular tissues, whereas propranolol treatment decreased the HIF-1α level in hemangioma tissues in a time- and dose-dependent manner. Moreover, propranolol treatment significantly decreased cell proliferation, migration and tube formation as well as promoted cell apoptosis in HIF-1α overexpression and knockdown hemangioma cells. Propranolol suppressed the cells proliferation, migration and tube formation of hemangioma cells through HIF-1α dependent mechanisms. HIF-1α could serve as a novel target in the treatment of hemangiomas.

Correlation research on the protein expression (p75NTR, bax, bcl-2, and caspase-3) and cortical neuron apoptosis following mechanical injury in rat.

OBJECTIVE: In this study, we aimed to survey the role of p75NTR, bax, bcl-2, and caspase-3 in the progress of traumatic brain injury (TBI). MATERIALS AND METHODS: A mechanical trauma model of vital neurons was established by putting external pressure, contusion and centrifugal acceleration on neurons. Morphological change, survival rate, assay of LDH activity, and apoptosis rate were evaluated for mild, medium and severe injury models. The expression of bax, bcl-2, caspase-3, p75NTR, p75NTR mRNA was determined by immunohistochemistry, immunofluorescence, Western blotting and RT-PCR. RESULTS: There was a transient high level Bcl-2 protein within 2 h after injury to increase neuronal tolerance and avoid apoptosis. Subsequently p75NTR, Bax/Bcl-2, and Caspase-3 reached their peaks from 48 to 72 h accompanied with the maximum apoptosis rate. CONCLUSIONS: Our results suggest that apoptosis ratio in varying degree injury groups are correlated with the expression level of p75NTRmRNA, p75NTR, Caspase-3, Bax/Bcl-2 ratio.

SKLB-287, a novel oral multikinase inhibitor of EGFR and VEGFR2, exhibits potent antitumor activity in LoVo colorectal tumor model.

Colorectal cancer (CRC) is the third common cancer and most of the chemotherapies of CRC currently used often suffer limited efficacy and large side effects. Targeted small-molecule by anti-tumor drugs are thought a promising strategy for improving the efficacy and reducing the side effects. In this investigation, we report a novel multikinase inhibitor, termed SKLB-287, which was discovered by us recently. SKLB-287 could efficiently inhibit the activation of endothelial growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2). It displayed very good anti-proliferative activity against LoVo CRC cells and considerable antiangiogenic potency in transgenic zebrafish embryos. Oral administration of SKLB-287 resulted in dose-dependent suppression of tumor growth in LoVo xenograft mouse model. Immunohistochemistry was adopted to examine the in vivo anti-tumor mechanism of action of SKLB-287.

A clinical study of pingyangmycin sclerotherapy for venous malformation: an evaluation of 281 consecutive patients.

WHAT IS KNOWN AND OBJECTIVE: In China, lidocaine together with 2 mg/mL of pingyangmycin (PYM, also known as bleomycin A5) is recommended for the treatment of venous malformations (VMs). The purpose of this study was to investigate whether lidocaine has a synergistic effect with PYM in improving the therapeutic outcomes of patients with VMs. Additionally, this study aimed to evaluate the outcomes of sclerotherapy for VMs using an intralesional injection of a low concentration of PYM (0·5 mg/mL). METHODS: A total of 281 patients with VMs were treated with 0·5 or 2 mg/mL of PYM with or without lidocaine and dexamethasone (DEX). All of the patients received a direct intralesional injection at a rate of 1 mL/min, and the volume of the solution varied from 1·5 to 6·0 mL per injection. RESULTS AND DISCUSSION: No significant differences were observed in the clinical outcomes between the PYM and PYM + lidocaine treatment groups (P > 0·05). The clinical outcomes were similar between the groups that were treated with 0·5 and 2 mg/mL of PYM, but the swelling and pain in the patients who were treated with 0·5 mg/mL of PYM were less severe compared with the patients who were treated with 2 mg/mL of PYM. A total of 29 patients with VM lesions on the glans penis were treated with 0·5 mg/mL of PYM + 0·5% lidocaine. Of these patients, 26 were cured, whereas three experienced a marked improvement. WHAT IS NEW AND CONCLUSION: Lidocaine does not have a synergistic effect with PYM in improving the therapeutic outcomes of patients with VMs. Sclerotherapy with a low concentration of PYM (0·5 mg/mL) combined with lidocaine and DEX is a safe and effective therapy for small superficial VMs of critical organs, such as the lips and the glans penis.

Using silicon nanowire devices to detect adenosine triphosphate liberated from electrically stimulated HeLa cells.

In this study, we used a biosensor chip featuring Abl tyrosine kinase-modified silicon nanowire field-effect transistors (SiNW-FETs) to detect adenosine triphosphate (ATP) liberated from HeLa cells that had been electrically stimulated. Cells that are cultured in high-ionic-strength media or buffer environments usually undermine the sensitivity and selectively of SiNW-FET-based sensors. Therefore, we first examined the performance of the biosensor chip incorporating the SiNW-FETs in both low- and high-ionic-strength buffer solutions. Next, we stimulated, using a sinusoidal wave (1.0 V, 50 Hz, 10 min), HeLa cells that had been cultured on a cell-culture chip featuring interdigitated electrodes. The extracellular ATP concentration increased by ca. 18.4-fold after electrical stimulation. Finally, we detected the presence of extracellular ATP after removing a small amount of buffer solution from the cell-cultured chip and introducing it into the biosensor chip.

Identification of SARS-COV spike protein-derived and HLA-A2-restricted human CTL epitopes by using a new muramyl dipeptidederivative adjuvant.

Severe acute respiratory syndrome (SARS) spread during the winter of 2003, and attempts have been made to develop vaccines against SARS corona virus (SARS-CoV). The present study provides a strategy to rapidly identify SARS-CoV-derived antigenic peptides recognized by HLA-A2-restricted cytotoxic T lymphocytes (CTLs). Forty-three candidate peptides having HLA-A2-binding motifs were selected in silico and HLA-A2/Db chimeric MHC class I-transgenic mice were immunized with these peptides and a new derivative of muramyl dipeptide that can induce upregulation of HLA-DR, CD80, CD86, and CD40 in human CD14+ antigen presenting cells, was administered as an adjuvant. Six HLAA2-restricted mouse CTL epitopes were identified, including two new epitopes which have never been reported before. One of the novel peptides was naturally processed and successfully induced HLAA2-restricted specific CTLs in both HLA transgenic mice and healthy donors. The method was useful, convenient and efficient for rapid identification of CTL epitopes derived from SARS-CoV proteins and will be possibly applicable for other pathogens to develop a peptide-based vaccine.

Effect of breastfeeding on asthma, lung function and bronchial hyperreactivity in ISAAC Phase II.

The association between breastfeeding and wheezing, lung function and atopy was evaluated in the International Study of Asthma and Allergy in Childhood (ISAAC) Phase II. Cross-sectional studies were performed in 27 centres in 20 countries. Information on disease and exposure factors was collected by parental questionnaires. Data from 54,000 randomly selected school children (aged 8-12 yrs, 31,759 with skin prick testing) and a stratified subsample (n = 4,888) were used for testing the correlation of breastfeeding with bronchial hyperreactivity and lung function. Random effect models for meta-analysis were applied to calculate combined odds ratios (ORs). Any breastfeeding was associated with less wheeze both in affluent (adjusted OR (OR(adj)) 0.87, 95% confidence interval (CI) 0.78-0.97) and nonaffluent countries (OR(adj) 0.80, 95% CI 0.68-0.94). Further analyses revealed that this was true only for nonatopic wheeze in nonaffluent countries (OR(adj) 0.69, 95% CI 0.53-0.90). Breastfeeding was not associated with atopic wheeze and objective measures of allergy in both affluent and nonaffluent countries. In contrast, breastfeeding was associated with higher predicted forced expiratory volume in one second in affluent countries only (mean ratio 1.11, 95% CI 1.02-1.20). Breastfeeding is associated with protection against nonatopic wheeze, which becomes particularly evident in nonaffluent countries. Overall, breastfeeding was not related to any measure of allergy. These findings may explain some of the controversy regarding breastfeeding, since the direction of the association with breastfeeding depends on the predominating wheeze phenotype (e.g. atopic, nonatopic).

Glucocorticoids inhibit degranulation of mast cells in allergic asthma via nongenomic mechanism.

BACKGROUND: Glucocorticoids (GCs) are the most potent anti-inflammatory agents available for allergic diseases including asthma, which are routinely believed to need several hours to take effect through regulating gene expression. Our previous report had shown that GCs could inhibit allergic asthma within 10 min, which the classical mechanism could not explain. OBJECTIVE: To confirm the existence and verify the sites of GCs' rapid action, we investigated nongenomic effects of GCs on degranulation of mast cells in allergic asthma. METHODS: The GCs' rapid action on airway mast cells deregulations was evaluated in the allergic asthma model of guinea pigs by the computer-assisted morphometry. Using whole-cell patch clamp and fluorometric assay, we examined GCs' nongenomic effect on IgE-mediated exocytosis and histamine release of rat basophilic leukaemia-2H3 mast cells. Employing the flash photolysis technique, we studied the role of Ca(2+) signal in the GCs' nongenomic effect. RESULTS: Inhaled GCs significantly inhibited airway mast cells degranulation in the allergic asthma model of guinea pigs within 10 min. In vitro, GCs could rapidly inhibit IgE-mediated exocytosis and histamine release of mast cells, and neither GC nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action. We further demonstrated that GCs' nongenomic effect was not through direct action on secretory machinery, but was mediated by a reduction in the [Ca(2+)](i) elevation. CONCLUSIONS: The study suggested for the first time that nongenomic pathway was involved in GCs' rapid inhibition on allergic asthma, and raised the possibility of new therapeutic strategies for allergic diseases including asthma.

Rapid inhibitory effect of corticosterone on histamine release from rat peritoneal mast cells.

Glucocorticoids are steroids endowed with powerful anti-inflammatory properties, which are routinely believed to require several hours to take effect through modulation of gene expression. Our recent report has shown that glucocorticoids could inhibit allergic reaction within 10 minutes, which the classical genomic mechanism could not explain. Histamine is thought to be one of major mediators in the allergic reaction, and IgE-mediated histamine release from mast cells plays a pivotal role in allergic diseases. Here, we have determined a rapid effect of corticosterone on histamine release from rat peritoneal mast cells, using fluorometric assay. The results showed that corticosterone could inhibit antigen-induced histamine release from rat peritoneal cells within 15 minutes (p<0.05), which could be mimicked by membrane-impermeable BSA conjugated corticosterone (p<0.05). Neither glucocorticoid nuclear receptor antagonist nor protein synthesis inhibitor could block the rapid action (p<0.05). The study provided evidence that nongenomic mechanism might be involved in rapid effect of glucocorticoids on mast cells in allergic disease.

Hyperbaric oxygen treatment attenuated the decrease in regional glucose metabolism of rats subjected to focal cerebral ischemia: a high resolution positron emission tomography study.

Cerebral hypoxia may be the main component of cell damage caused by ischemia. Previous studies demonstrated a neuroprotective effect of early hyperbaric oxygen (HBO) treatment in various animal models of focal cerebral ischemia. Neuropathologic study showed that exposure of HBO may prevent cell death in ischemic cortex. In the present study, we aimed to assess cellular function of ischemic rat brain after HBO treatment by means of a high-resolution positron emission tomography scanner (microPET) used specifically for small animal imaging. The male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO), with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. One hour after ischemia, HBO therapy (3 atm absolute, 1 h) was initiated. Local cerebral glucose utilization in the ischemic area was measured before, 1 h and 3 h after ischemia, with 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) as a tracer. Neurological deficits and infarct volumes were assessed at 24 h after ischemia. Our study showed that early HBO therapy significantly reduced infarct volume of brain 24 h after ischemia. Moreover, glucose utilization in the ischemic area underwent a severe decrease during 1-3 h after MCAO, while the early HBO treatment significantly attenuated the decrease in cerebral metabolic rate of glucose in the ischemic core of the cortex compared with controls. We report for the first time the application of microPET to quantify the rates of glucose metabolism in the ischemic core of rats exposed to HBO. Our results suggest that the early exposure of HBO can partially reverse the downward trend for glucose utilization in the ischemic core, which might contribute to the reported beneficial effects of early HBO therapy on permanent cerebral ischemia.

Pharmacologic and anti-IgE treatment of allergic rhinitis ARIA update (in collaboration with GA2LEN).

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Diterpenoids from isodon eriocalyx

Three new diterpenoids, eriocalyxins C-E (1-3), were isolated from Isodon eriocalyx. Their structures were elucidated as 6beta-hydroxy-15beta-acetoxy-3alpha,20-epoxy-16beta, 17-epoxy-ent-kaur-1,7-dione (1), 1alpha,7beta-dihydroxy-6beta, 15beta-diacetoxy-7,20-epoxy-ent-kaur-16-ene (2), and 15beta-acetoxy-1,6-dioxo-6,7-seco-ent-kaur-2,16-dien-7,20-olide (3), respectively, by means of spectroscopic methods, including one- and two-dimensional NMR techniques.

Interactions between senescence and leaf orientation determine in situ patterns of photosynthesis and photoinhibition in field-grown rice

Photosynthesis and photoinhibition in field-grown rice (Oryza sativa L.) were examined in relation to leaf age and orientation. Two varieties (IR72 and IR65598-112-2 [BSI206]) were grown in the field in the Philippines during the dry season under highly irrigated, well-fertilized conditions. Flag leaves were examined 60 and 100 d after transplanting. Because of the upright nature of 60-d-old rice leaves, patterns of photosynthesis were determined by solar movements: light falling on the exposed surface in the morning, a low incident angle of irradiance at midday, and light striking the opposite side of the leaf blade in the afternoon. There was an early morning burst of CO2 assimilation and high levels of saturation of photosystem II electron transfer as incident irradiance reached a maximum level. However, by midday the photochemical efficiency increased again almost to maximum. Leaves that were 100 d old possessed a more horizontal orientation and were found to suffer greater levels of photoinhibition than younger leaves, and this was accompanied by increases in the de-epoxidation state of the xanthophyll cycle. Older leaves had significantly lower chlorophyll content but only slightly diminished photosynthesis capacity.

Flexuosol A, a new tetrastilbene from vitis flexuosa

A novel tetrastilbenoid, flexuosol A (1), was isolated from the stems of Vitis flexuosa together with the known gnetin A, (+)-epsilon-viniferin, vitisin A, and hopeaphenol. The structure of 1 was elucidated using spectral methods.