[Effects of cinepazide maleate injection on blood pressure in patients with acute ischemic stroke and hypertension].

Objective: To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection. Methods: This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes. Results: This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%,P>0.05) between cinepazide maleate group and control group. Conclusion: Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

[Epidemiology of chronic cough in China: current status and future perspective].

Chronic cough is one of the most common major complaints in medical outpatient. Chronic cough not only seriously affects quality of personal life, but also burdens public health. Large-scale and high-quality epidemiological study on chronic cough has not been carried out in China, and relevant reviews are also lacking. Therefore, based on the studies concerning epidemiology of chronic cough in China, we reviewed the prevalence, risk factors, etiology, quality of life and economic burden. In addition, future perspectives and reasonable suggestions for the development of epidemiology of chronic cough were also proposed.

[Chronic cough in China: progress and perspectives].

Great progress has been made in regard of mechanism, etiological diagnosis and treatment of chronic cough since the beginning of the 20th century, and Chinese guidelines of diagnosis, management of cough was developed. Moreover, Chinese experts also participated in the formulation of international cough guidelines. Through the promotion of the guidelines, the level of diagnosis and treatment of chronic cough has been significantly improved in China. In the future, we should strengthen the studies on the epidemiology of chronic cough, the central regulation of chronic cough, and the treatment of refractory chronic cough, and promote the cough guidelines in primary community hospitals.

[Menopausal symptoms and quality of life of hormone receptor positive breast cancer patients at different endocrine therapy time].

Objective: To explore the menopausal symptoms and quality of life of hormone receptor positive (HR+ ) breast cancer patients at different endocrine therapy time. Methods: The HR+ breast cancer patients who were pathologically confirmed from 2011 to 2017 in the Sichuan Cancer Hospital were divided into three groups according to endocrine therapy time (<12 months, 12~36 months, >36 months) and analyzed by a cross-sectional study. The Menopausal symptoms and quality of life of these patients were measured using the modified Kupperman scale and the functional assessment of cancer therapy-breast cancer (FACT-B) scale. The differences of menopausal symptoms among different time groups and drug groups were analyzed by Chi-square test. The differences of quality of life and the effects of menopausal symptoms on quality of life were tested by covariance and multiple linear regression analyses. Results: The average score of menopausal symptom of 167 patients was 14.5±7.6 and the prevalence rate was 87.4% (146/167). Among all of the menopausal symptoms, the prevalence rate of insomnia was the highest (73.7%, 123/167). Besides insomnia and excitement, hot flashes was more prevalent in selective estrogen receptor modulator (SERM) users (64.8%, 79/122) , while osteoarthritis was more prevalent in aromatase inhibitor (AI) users (62.2%, 28/45). The total score of FACT-B of Patients was 104.5±15.5, and the compliance rate was up to 89.8% (150/167). However, the condition of each dimension was different, the compliance rates of social/ family and functional dimension were lowest, which were 73.0% (122/167) and 50.9% (85/167), respectively. The menopausal symptoms of patients at different time groups were 15.0±1.3, 14.0±6.9, 14.5±7.4, respectively, and the total score of FACT-B of patients at different time groups were 102.7±17.8, 105.0±12.9, 105.6±16.7, respectively, without significant differences (both P>0.05). Multiple linear regression analysis showed that menopausal symptoms impaired the quality of life of SERM users during the endocrine therapeutic period. The standardized regression coefficients of three time groups were -0.67, -0.30, -0.50, respectively, with the lowest effect on 12~36 months group. Conclusion: HR+ breast cancer patients will have a poor function recovery and social/ family return, who need more attention. Menopausal symptoms are common problems during endocrine therapy, and active measures should be taken to improve patients' quality of life.

Selective release of muscle-specific, extracellular microRNAs during myogenic differentiation.

MyomiRs are muscle-specific microRNAs (miRNAs) that regulate myoblast proliferation and differentiation. Extracellular myomiRs (ex-myomiRs) are highly enriched in the serum of Duchenne Muscular Dystrophy (DMD) patients and dystrophic mouse models and consequently have potential as disease biomarkers. The biological significance of miRNAs present in the extracellular space is not currently well understood. Here we demonstrate that ex-myomiR levels are elevated in perinatal muscle development, during the regenerative phase that follows exercise-induced myoinjury, and concomitant with myoblast differentiation in culture. Whereas ex-myomiRs are progressively and specifically released by differentiating human primary myoblasts and C2C12 cultures, chemical induction of apoptosis in C2C12 cells results in indiscriminate miRNA release. The selective release of myomiRs as a consequence of cellular differentiation argues against the idea that they are solely waste products of muscle breakdown, and suggests they may serve a biological function in specific physiological contexts. Ex-myomiRs in culture supernatant and serum are predominantly non-vesicular, and their release is independent of ceramide-mediated vesicle secretion. Furthermore, ex-myomiRs levels are reduced in aged dystrophic mice, likely as a consequence of chronic muscle wasting. In conclusion, we show that myomiR release accompanies periods of myogenic differentiation in cell culture and in vivo. Serum myomiR abundance is therefore a function of the regenerative/degenerative status of the muscle, overall muscle mass, and tissue expression levels. These findings have implications for the use of ex-myomiRs as biomarkers for DMD disease progression and monitoring response to therapy.

A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network.

Aberrant stem cell-like gene regulatory networks are a feature of leukaemogenesis. The ETS-related gene (ERG), an important regulator of normal haematopoiesis, is also highly expressed in T-ALL and acute myeloid leukaemia (AML). However, the transcriptional regulation of ERG in leukaemic cells remains poorly understood. In order to discover transcriptional regulators of ERG, we employed a quantitative mass spectrometry-based method to identify factors binding the 321 bp ERG +85 stem cell enhancer region in MOLT-4 T-ALL and KG-1 AML cells. Using this approach, we identified a number of known binders of the +85 enhancer in leukaemic cells along with previously unknown binders, including ETV6 and IKZF1. We confirmed that ETV6 and IKZF1 were also bound at the +85 enhancer in both leukaemic cells and in healthy human CD34+ haematopoietic stem and progenitor cells. Knockdown experiments confirmed that ETV6 and IKZF1 are transcriptional regulators not just of ERG, but also of a number of genes regulated by a densely interconnected network of seven transcription factors. At last, we show that ETV6 and IKZF1 expression levels are positively correlated with expression of a number of heptad genes in AML and high expression of all nine genes confers poorer overall prognosis.

Selective effects of fenitrothion on murine splenic T-lymphocyte populations and cytokine/granzyme production.

The aim of this study was to investigate in vitro effects of fenitrothion (FNT) on mouse splenic lymphocytes. Here, naïve mice had their spleens harvested and splenocytes isolated. After exposure to FNT for 48 hr: splenocyte viability was measured using a tetrazolium dye assay; cell phenotypes, i.e., B-cells (CD19+), T-cells (CD3+), and T-cell subsets (CD4+ and CD8+), were quantified by flow cytometry; and, production of cytokines/granzyme-B was assessed via enzyme-linked immunosorbent assay. The ability for FNT to induce oxidative stress in the cells was evaluated by measuring hydroxyl radical (·OH) and malondialdehyde (MDA) production and changes in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity. The results showed that FNT significantly inhibited splenocyte proliferation, and decreased production of interleukin (IL)-2, interferon gamma, IL-4, and granzyme B, but had no impact on IL-6 production. FNT also selectively decreased splenic T-cell levels but did not induce changes in CD19+ B-cells. Further, within the T-cell populations, percentages of CD3+, CD4+, and CD8+ T-cells (particularly CD8+ T-cells) were reduced. Lastly, FNT selectively increased MDA and ·OH production and inhibited SOD and GSH-Px activities in the splenic lymphocytes. These findings suggest that, due to oxidative damage, FNT selectively inhibits splenic T-lymphocyte survival and cytokine/granzyme production in vitro.

[Association of plasma leptin levels and soluble leptin receptor with breast cancer].

Objective: To explore the association between plasma leptin (LEP) levels, soluble leptin receptor(SLR), free leptin index and breast cancer. Methods: 245 new female cases of primary breast cancer confirmed by histopathology examination were sequentially recruited into the study. A total of 245 age-matched healthy women were enrolled as controls during the same period. A standardized questionnaire was used to collect the demographic information of the subjects. Blood samples were collected and the levels of LEP and SLR in plasma were measured by enzyme linked immunosorbent assay. The differences of LEP, SLR and FLI expression between control and cases group, as well as different breast cancer subtypes and TNM stages were compared using t-test and ANOVA after stratification by menopause status. Multivariate logistic regression was used to explore the contributions of the three indexes to the risk of breast cancer. Results: Females in both cases and control group were (50.7 ± 9.4) years old. The level of SLR and FLI (P(50)(P(25),P(75))) in premenopausal women were 18.4 (11.2, 28.7), 0.5 (0.4, 0.6) µg/L in case group and 27.7 (19.2, 43.4), 0.3 (0.3, 0.4) µg/L in control group (P<0.001). While the level of postmenopausal women in case group were 20.3 (12.8, 31.8), 0.5 (0.4, 0.6) µ g/L (P<0.001), and 30.1 (18.8, 40.5), 0.3 (0.3, 0.5) µg/L in control group (P<0.001), respectively. After adjustment for confounding factors and BMI, the relationship between FLI and breast cancer remained significant for both pre- and postmenopausal women while the association between SLR and breast cancer was significant only in premenopausal women. Compared with the lowest level of SLR, higer levels of SLR is associated with a reduced risk of breast cancer (premenopausal women, OR=0.10, 95% CI: 0.04-0.29, P(trend)<0.001). Compared with the lowest level of FLI, FLI at higher levels is associated with an increased risk of breast cancer (premenopausal women, OR=7.14, 95% CI: 2.86-17.83, P(trend)<0.001; postmenopausal women, OR=8.10, 95% CI: 2.85-22.98, P(trend)<0.001). No significant association between LEP and breast cancer or association between the three indexes and breast cancer subtypes and TNM stages was found (P>0.05). Conclusion: SLR may be a protective factor for breast cancer while FLI may increase the risk of breast cancer.

Cathelicidin-encoding Lactococcus lactis promotes mucosal repair in murine experimental colitis.

BACKGROUND AND AIM: The preventive effect of intrarectal administration of mouse cathelicidin (mCRAMP) and oral administration of mCRAMP-encoding Lactococcus lactis (N4I) has been shown in murine experimental colitis. It is pivotal to understand the ability of N4I whether it can promote mucosal repair in existing colitis. METHODS: Mice with dextran sulfate sodium-induced ulcerative colitis (UC) were treated orally with L. lactis or its transformed strain with or without nisin induction. The body weight, clinical symptoms, and histological changes of colonic tissues were determined. Sulfasalazine was used as a reference drug. Young adult mouse colon cells were used to further elucidate the direct action and possible mechanisms of mCRAMP to promote colonic wound repair. RESULTS: Results showed that N4I could improve the clinical symptoms, maintain crypt integrity and preserve mucus-secreting layer in colitis animals. The preparation also could prevent cell death and promote cell proliferation. In contrast, effective dose of sulfasalazine only alleviated clinical symptoms but not the mucosal damage and repair in the colon. In vitro study further showed that mCRAMP could directly promote wound repair by accelerating cell migration but not cell proliferation through the GPCR/MAPK pathway. CONCLUSIONS: mCRAMP-encoding L. lactis could be a potential therapeutic preparation better than the traditional anti-inflammatory agent in the treatment of UC.

MiR-26a regulates vascular smooth muscle cell calcification in vitro through targeting CTGF.

Vascular calcification is one of the most important factors for high morbidity and mortality from cardiovascular and cerebrovascular diseases. The aim of this study is to investigate the effect and mechanism of miR-26a on vascular smooth muscle cell calcification. First, the VSMCs were induced by ß-glycerol phosphate (ß-GP) for 7d and 14d, and Alizarin Red S staining was performed to examine the mineralized nodule change; then real time RT-PCR and western blotting were performed to explore the expression of miR-26a, CTGF, OPG, RANKL and ALP in un-induced and ß-GP-induced VSMCs; next, the VSMCs were transfected with miR-26a mimics, and Alizarin Red S staining was performed to examine the mineralized nodule change; finally, real time RT-PCR and western blotting were performed to explore the expression of miR-26a, CTGF, OPG, RANKL and ALP in un-transfected and miR-26a mimics transfected VSMCs. After ß-GP treatment, ß-GP promoted clear mineralized nodule changes, and miR-26a and OPG expression were significantly decreased and CTGF, RANKL and ALP expression were increased in VSMCs. Overexpression of miR-26a inhibited VSMCs calcification induced by ß-GP, and regulated the expression of CTGF, OPG, RANKL and ALP. Our findings suggested that up-regulation of miR-26a before ß-GP treatment inhibits VSMCs calcification through targeting CTGF (Fig. 4, Ref. 18).

Left Ventricular Lead Fracture 6 Years after Implantation with a Retained Guidewire.

We reported a case that left ventricular (LV) lead with retained guidewire was used 6 years ago, but the LV lead was broken during 6 years of follow-up. Although the retained guidewire technique has already been abandoned, the long-term safety of retained guidewire lead appears to be an even greater concern.

[Efficacy observation of (125)I seed implantation therapy for locoregional recurrent and metastatic breast cancer].

OBJECTIVE: To assess the efficacy and side effects of (125)I seed implantation for locoregional recurrent and metastatic breast cancer, and to discuss its role in the comprehensive therapy of breast cancer. METHODS: Forty-three patients with locoregional recurrent or metastatic breast cancer were included in this study. They received (125)I seed implantation and were followed up to evaluate the efficacy and adverse reactions of the treatment. RESULTS: Among 54 lesions in the 43 cases, there were complete response (CR) in 39, partial response (PR) in 13, stable disease (SD) in 2 patients, with a response rate of 96.3%. All 17 cases with local pain achieved pain relief. With a median follow up of 36 months (range 14 to 60 months), the 1-, 3-, and 5-year local control rate was 85.2%, 53.7% and 1.9%, and the 1-, 3-, and 5-year survival rate was 95.3%, 67.4% and 37.2%, respectively. No serious radiotherapy side effect was observed. CONCLUSION: In patients with unresectable locoregional recurrent or metastatic breast cancer, (125)I seed implantation shows proved efficacy and few complications, and can be an important treatment option.

Dynamic properties of a metal photo-thermal micro-actuator.

This work presents the design, modeling, simulation, and characterization of a metal bent-beam photo-thermal micro-actuator. The mechanism of actuation is based on the thermal expansion of the micro-actuator which is irradiated by a laser, achieving noncontact control of the power supply. Models for micro-actuators were established and finite-element simulations were carried out to investigate the effects of various parameters on actuation properties. It is found that the thermal expansion coefficient, thermal conductivity, and the geometry size largely affected actuation behavior whereas heat capacity, density, and Young's modulus did not. Experiments demonstrated the dynamic properties of a Ni micro-actuator fabricated via LIGA technology with 1100/30/100 µm (long/wide/thick) arms. The tip displacement of the micro-actuator could achieve up to 42 µm driven by a laser beam (1064 nm wavelength, 1.2 W power, and a driving frequency of 1 HZ). It is found that the tip displacement decreases with increasing laser driving frequency. For 8 Hz driving frequency, 17 µm (peak-valley value) can be still reached, which is large enough for the application as micro-electro-mechanical systems. Metal photo-thermal micro actuators have advantages such as large displacement, simple structure, and large temperature tolerance, and therefore they will be promising in the fields of micro/nanotechnology.

Ultrasonic imaging of gunshot wounds in pig limb.

We investigated wound tract extension of traumatic gunshot wounds in limb soft tissues as well as wound tract sonographic features and change-patterns when the limb position was changed. The experimental animals included 8 healthy crossbred pigs in the Chengdu plain region. Chinese Type 53 Carbine was used to establish the gunshot wound model of porcine soft tissues. Gunshot-injured zones in the soft tissues were dynamically observed at different time points using ultrasonic technology. Pathological examinations were performed for the corresponding regions for comparison and analysis. The internal echo of the wound tract was a pipe-like echo that changed over time. The wound tract extension changed with postural changes. The gas echo extended along the inside of the wound track, surrounding the fascia to further tissues. Ultrasonic imaging of gunshot wounds in pig soft tissues shows specific characteristics. The application of ultrasound technology may provide important imaging protection for gunshot wound debridement and postoperative unobstructed drainage, helping to improve the judgment and treatment of limb gunshot injuries.

Sandwich assay for tacrolimus using 2 antitacrolimus antibodies.

BACKGROUND: Although detection of natural haptens by antihapten antibodies in sandwich assay format has the theoretical advantages of high analytical specificity and sensitivity, this type of assay has not been reported because of the seemingly insurmountable task of avoiding steric hindrance between the 2 bindings. This is especially true for ring-structured hydrophobic haptens. The macrolide drug tacrolimus (FK506, Prograf®, 804 Da) is such a hapten. Here we show the detection of tacrolimus using 2 antitacrolimus monoclonal antibodies in a sandwich assay. METHODS: Both antibodies were developed by use of an intact tacrolimus molecule covalently linked to a carrier protein but via 2 different positions separated by 10 carbon atoms. Epitope analysis based on drug analog binding was used to show no overlap between the binding sites of the 2 antibodies, indicating the 10-carbon separation resulted in 2 distinct epitopes. The distinct epitopes suggested that the drug might be approachable by the antibodies from 2 separate directions, which predicted simultaneous binding as in sandwich formation. RESULTS: This prediction was confirmed in sandwich ELISA and affinity column-mediated immunoassay formats. The assay demonstrated good imprecision and significantly lower metabolite cross-reactivity than competitive assay counterparts. Comparison with liquid chromatography-tandem mass spectrometry (LC-MS/MS) using 55 whole-blood samples from transplant patients with tacrolimus concentrations ranging from 0.9 to 29.5 ng/mL showed a linear regression: sandwich = 0.99 × LC-MS/MS + 0.10 ng/mL, r = 0.991, Sy|x = 1.08 ng/mL. CONCLUSIONS: This work demonstrates that a highly specific sandwich assay using 2 antihapten antibodies is feasible for the measurement of a hapten drug.

1,25-dihydroxyvitamin D3 augments low-dose PMA-based monocyte-to-macrophage differentiation in THP-1 cells.

The human monocytic THP-1 cell line is the most routinely employed in vitro model for studying monocyte-to-macrophage differentiation. Despite the wide use of this model, differentiation protocols using phorbol 12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D3 (1,25D3) vary drastically between studies. Given that differences in differentiation protocols have the potential to impact the characteristics of the macrophages produced, we aimed to assess the efficacy of three different THP-1 differentiation protocols by assessing changes in morphology and gene- and cell surface macrophage marker expression. THP-1 cells were differentiated with either 5 nM PMA, 10 nM 1,25D3, or a combination thereof, followed by a rest period. The results indicated that all three protocols significantly increased the expression of the macrophage markers, CD11b (p < 0.001) and CD14 (p < 0.010). Despite this, THP-1 cells exposed to 1,25D3 alone did not adopt the morphological and expression characteristics associated with macrophages. PMA was required to produce these characteristics, which were found to be more pronounced in the presence of 1,25D3. Both PMA- and PMA with 1,25D3-differentiated THP-1 cells were capable of M1 and M2 macrophage polarization, though the gene expression of polarization-associated markers was most pronounced in PMA with 1,25D3-differentiated THP-1 cells. Moreover, the combination of PMA with 1,25D3 appeared to support the process of commitment to a particular polarization state.

Microstructure change of ZnO nanowire induced by energetic x-ray radiation and its effect on the field emission properties.

The changes in the microstructure of ZnO nanowire were studied after exposure to different radiation doses of energetic x-rays. Detailed structural, composition and optical analyses were carried out. It was found that the surface composition changed and defects were formed in the irradiated ZnO nanowires. The structural change of ZnO nanowires after thermal treatment was also studied and similar defects were observed. It is proposed that phonon-induced localized heating is the main reason for the observed changes in microstructure. Finally, the field emission properties of ZnO nanowires before and after x-ray radiation were studied. It was found that the increase of work function and change in morphology induced by the irradiation were the reasons for the observed change in field emission properties.

Postural sway and rhythmic electroencephalography analysis of cortical activation during eight balance training tasks.

BACKGROUND: The purpose of this study was to investigate the changes in the Power Spectrum Density (PSD) of the electroencephalography (EEG) in common sensorimotor balance training tasks of varying difficulty. Sensorimotor balance exercises including alteration of vision, base of support or surface compliance are used to improve postural control. These exercises are presumed to induce supraspinal adaptation, however, there were no studies that investigated the power changes of the cortical activity in these static balance tasks. Our objective was to provide evidence in the cortical involvement with the static balance tasks frequently used in sensorimotor training. MATERIAL AND METHODS: Postural sway and EEG changes of alpha, beta and sigma wave bands were measured in seventeen participants during eight balance tasks of varying difficulty with eyes open and closed, feet in tandem or apart and on foam or a firm surface. RESULTS: The power of beta and sigma bands increased significantly at the parietal and central area of the brain in tasks with eyes open together with one sensory factor (base of support or surface compliance) or two sensory factors (base of support and surface compliance) altered, and in task with three sensory factors (vision, base of support and surface compliance) altered from the control task. CONCLUSIONS: This study demonstrated the cortical involvement in the sensorimotor balance tasks, suggesting that these exercises may induce cortical adaptation for postural control. The results support subcortical control with increased task difficulty and the increase in cortical processing when task became extremely challenging.

Antibodies against Periodontal Microorganisms and Cognition in Older Adults.

INTRODUCTION: Markers of poor oral health are associated with impaired cognition and higher risk of Alzheimer disease (AD) and thus may help predict AD. OBJECTIVES: The aim of this study was to evaluate the cross-sectional association between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and cognition in middle-aged and older adults. METHODS: The study population consisted of participants of the third National Health and Nutrition Examination Survey (NHANES III) (1988 to 1994), who were 60 y and older, among whom cognition and IgG antibodies against 19 periodontal microorganisms were measured (N = 5,162). RESULTS: In multivariable quantile regression analyses, the Orange-Red (Prevotella melaninogenica, Prevotella intermedia, Prevotella nigrescens, Porphyromonas gingivalis) and Yellow-Orange (Staphylococcus intermedius, Streptococcus oralis, Streptococcus mutans, Fusobacterium nucleatum, Peptostreptococcus micros, Capnocytophaga ochracea) cluster scores were negatively associated with cognition. A 1-unit higher cluster score for the Orange-Red cluster was associated on average with a lower cognitive score (ß for 30th quantile = -0.2640; 95% confidence interval [CI], -0.3431 to -0.1848). Similarly, a 1-unit higher score for the Yellow-Orange cluster was associated with a lower cognitive score (ß for 30th quantile = -0.2445; 95% CI, -0.3517 to -0.1372). CONCLUSION: Groups of IgG antibodies against periodontal microorganisms were associated with lower cognition among free living adults 60 years and older, who were previously undiagnosed with cognitive impairment. Though poor oral health precedes the development of dementia and AD, oral health information is currently not used, to our knowledge, to predict dementia or AD risk. Combining our findings with current algorithms may improve risk prediction for dementia and AD. KNOWLEDGE TRANSLATION STATEMENT: IgG antibodies against periodontal microorganisms were associated with lower cognition among adults 60 years and older previously undiagnosed with cognitive impairment. Periodontal disease may predict cognition among older adults.