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To investigate histopathological placental lesions and adverse neonatal outcomes by Pre-eclampsia (PE) with Gestational Diabetes Mellitus (GDM).This was a retrospective cohort study of pregnancies with PE delivered between 1 January 2012 to 1 January 2014. Pregnant women with PE were recruited, and divided into PE with GDM (PE + GDM) group (The (PE + GDM) group was significantly associated with high placenta weight (534.8 ± 124.1 vs 519.3 ± 132.3 g,GDM increased the offspring's complication in pregnancy with PE, the potential mechanism might be that GDM increased the placenta inflammation.

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies directed against different components of the neuromuscular junction (NMJ), and pathogenic mechanism associated thymic pathologies. Microbiota invading thymus is hypothesized to trigger human autoimmune response by providing antigens to produce NMJ antibodies and clinical manifestations of myasthenia gravis. There are many reports of microbial nucleic acid isolation and protein expression and even a few studies of viable microbes isolated from the human thymus. However, high-resolution investigation of microbial infectious agents from the human thymus that may contribute to myasthenia gravis is very limited. To investigate potential microbial infection within human thymus tissue samples, we performed quantitative real-time PCR of the bacterial 16S ribosomal RNA (rRNA) and fungal 18S rRNA gene analysis on (1) a total of 23 abnormal thymus including 13 thymomas and 4 thymus hyperplasias obtained from MG patients and 6 thymoma-nonMG patients who underwent thymectomy. (2) Another 14 normal thymus were selected as control from patients who underwent congenital heart disease surgery. Results show that a wide range of bacteria agents are exhibited in the thymus, rather than fungus. And an intriguing new observation that shows the microbiota displayed differences among MG patients, thymoma-nonMG patients, and normal thymus as judged from the taxonomic profiles in these three groups. Compared with the normal thymus group, the Klebsiella and Escherichia coli show higher abundance in MG patient group. The thymus harbors bacteria agents and Klebsiella and Escherichia coli may be potential pathogens associated with MG. Further investigations are needed to elucidate the possible associations of Klebsiella and E. coli and MG.

k nearest neighbor ( k NN) queries are frequently used in location-based services (LBSs), by which we wish to get k closest points of interest (POIs) given a certain point. Since the cloud computing is developing fast, LBS providers are tended to outsource spatial databases to the cloud. However, cloud servers are often untrusty, so that ensuring the spatial query integrity as well as the spatial query privacy is critical. We present a verifiable privacy-preserving k NN query scheme, which can be used on road networks. Our work makes use of the network Voronoi diagram and several cryptographic primitives including pseudo-random functions, Paillier cryptosystem, condensed RSA digital signature, and so on. It can simultaneously preserve the privacy of spatial data and k NN queries, and verify the reliability of query results. The effectiveness and practicability of our scheme are validated by our experimental results. We further analyzed the security of our scheme under the adaptive chosen-query attack via rigorous proof.

ObjectiveEarly life bronchiolitis has been hypothesised to be associated with the subsequent risk of persistent wheezing or asthma. However, the link remains controversial. The objective of our study was to evaluate the association between bronchiolitis before 2 years of age and the late-onset wheezing/asthma.DesignSystematic review and meta-analysis.MethodsPubMed, Embase and Web of Science databases were systematically searched for studies published between 1955 and January 2020. Meanwhile, we also checked through the reference lists of relevant articles to see whether these references included reports of other studies that might be eligible for the review. Cohort and case–control studies assessing the association between early-life bronchiolitis and late-onset wheezing/asthma were included in this meta-analysis. Data were extracted by two independent reviewers. Results were pooled using a random-effects model or fixed-effects model according to the heterogeneity among studies.Results32 original articles with 292 844 participants, which met the criteria, were included in this meta-analysis. Bronchiolitis before 2 years of age was associated with an increased risk of subsequent wheezing/asthma (relative risk=2.46, 95% CI 2.14 to 2.82, pConclusionsThe meta-analysis indicates an association between bronchiolitis before 2 years of age and the wheezing/asthma in later life. Well-designed and highly standardised prospective studies that better address bias due to potential confounding factors are needed to validate the risk identified in our meta-analysis.PROSPERO registration numberCRD42018089453.

Aim: The purpose of the present study was to explore the function and mechanism of tensin 1 (TNS1) in non-small cell lung cancer (NSCLC) progression. Methods: The expression of TNS1 in NSCLC cells and tissues was assessed by RT-PCR and Western blot. Besides, Kaplan–Meier survival analysis was recruited to explore the association between TNS1 and NSCLC. Cell growth was analyzed by MTT and flow cytometry assay, while cell metastasis was determined by wound healing and transwell assays. The targeting relationship between TNS1 and miR-152 was assessed by luciferase activity assays. And Western blot was employed to determine the expression of related proteins of Akt/mTOR/RhoA pathway. Results: TNS1 level was boosted in NSCLC cells and tissues, related to the prognosis of NSCLC patients. Furthermore, it was proved that TNS1 promoted the growth and metastasis of NSCLC cells via Akt/mTOR/RhoA pathway. And miR-152 targeted TNS1 to affect the progression of NSCLC. Conclusion: miR-152/TNS1 axis inhibits the progression of NSCLC by Akt/mTOR/RhoA pathway.

Malignant peripheral nerve sheath tumor (MPNST) is a rare tumor that can develop on the lining of nerves and within the network of nerve fibers in different organs, and it is commonly found in the head and neck, limbs, and trunk. These tumors can occur in patients of any age. They most commonly occur in adults aged 20 to 50 years; however, fewer cases of this tumor in children have been reported. To date, no neonatal case of MPNST in the nasal cavity has been reported. Here, we report the case of a 4-day-old female newborn who presented with a nasal mass that re-enlarged after surgery and was diagnosed as MPNST of the nasal cavity on the basis of pathological results. This is the first report of MPNST in the nasal cavity of a neonate. Differential diagnosis and treatment of nasal masses have been proposed in the related literature.

To determine the long-term effect of maternal nicotine intake on the lung development of the offspring in adult life, we analyzed the alveolar structure, protein expression in the adult rat offspring lungs.We determined animal body weight (BW), lung weight (LW), lung/body weight ratio (L/BWR), lung volume (LV), radial alveolar count (RAC), alveolar septal thickness (AST) and expression of collagen, AT1R, AT2R, TGF-β1, pSmad3, Smad3 and CTGF proteins.Male offspring lung showed decreased RAC, thickened alveolar septa, increased collagen, AT1R, TGF-β1, pSmad3 and CTGF proteins. In contrast, female offspring lungs had reduced L/BWR, increased LV, and expression of AT2R, resulting in decreased AT1R to AT2R ratio.Maternal nicotine use during development programs abnormal lung development in male rats. This finding links maternal nicotine use to increased susceptibility to interstitial pulmonary fibrosis in adult male but not female offspring, indicating sex-dependent effects of developmental nicotine exposure.

Our previous study demonstrated that increased Ca 2+ -activated K + (BK Ca ) channel activity played a key role in the normal adaptation of reduced myogenic tone of uterine arteries in pregnancy. The present study tested the hypothesis that chronic hypoxia during gestation inhibits pregnancy-induced upregulation of BK Ca channel function in uterine arteries. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (≈300 m) or exposed to high-altitude (3801 m) hypoxia for 110 days. Hypoxia during gestation significantly inhibited pregnancy-induced upregulation of BK Ca channel activity and suppressed BK Ca channel current density in pregnant uterine arteries. This was mediated by a selective downregulation of BK Ca channel β1 subunit in the uterine arteries. In accordance, hypoxia abrogated the role of the BK Ca channel in regulating pressure-induced myogenic tone of uterine arteries that was significantly elevated in pregnant animals acclimatized to chronic hypoxia. In addition, hypoxia abolished the steroid hormone-mediated increase in the β1 subunit and BK Ca channel current density observed in nonpregnant uterine arteries. Although the activation of protein kinase C inhibited BK Ca channel current density in pregnant uterine arteries of normoxic sheep, this effect was ablated in the hypoxic animals. The results demonstrate that selectively targeting BK Ca channel β1 subunit plays a critical role in the maladaption of uteroplacental circulation caused by chronic hypoxia, which contributes to the increased incidence of preeclampsia and fetal intrauterine growth restriction associated with gestational hypoxia.

Uterine vascular tone significantly decreases whereas uterine blood flow dramatically increases during pregnancy. However, the complete molecular mechanisms remain elusive. We hypothesized that increased Ca 2+ -activated K + (BK Ca ) channel activity contributes to the decreased myogenic tone of uterine arteries in pregnancy. Resistance-sized uterine arteries were isolated from nonpregnant and near-term pregnant sheep. Electrophysiological studies revealed a greater whole-cell K + current density in pregnant compared with nonpregnant uterine arteries. Tetraethylammonium and iberiotoxin inhibited K + currents to the same extent in uterine arterial myocytes. The BK Ca channel current density was significantly increased in pregnant uterine arteries. In accordance, tetraethylammonium significantly increased pressure-induced myogenic tone in pregnant uterine arteries and abolished the difference in myogenic responses between pregnant and nonpregnant uterine arteries. Activation of protein kinase C produced a similar effect to tetraethylammonium by inhibiting BK Ca channel activity and increasing myogenic tone in pregnant uterine arteries. Chronic treatment of nonpregnant uterine arteries with physiologically relevant concentrations of 17β-estradiol and progesterone caused a significant increase in the BK Ca channel current density. Western blot analyses demonstrated a significant increase of the β1, but not α, subunit of BK Ca channels in pregnant uterine arteries. In accordance, steroid treatment of nonpregnant uterine arteries resulted in an upregulation of the β1, but not α, subunit expression. The results indicate that the steroid hormone-mediated upregulation of the β1 subunit and BK Ca channel activity may play a key role in attenuating myogenic tone of the uterine artery in pregnancy.

Cocaine abuse is a significant problem among pregnant women. The present study tested the hypothesis that prenatal cocaine exposure impairs myogenic reactivity of coronary arteries in adult offspring. Pregnant rats received cocaine (30 mg kg −1 day −1 ) or saline from days 15 to 21 of gestational age, and experiments were conducted in 3-month-old offspring. In pressurized coronary septal arteries, the diameter and vessel wall intracellular Ca 2+ concentrations were measured simultaneously in the same tissue as a function of intraluminal pressure. Cocaine did not affect KCl-induced contractions of coronary arteries in either males or females but decreased the distensibility in male vessels. In male offspring, cocaine treatment resulted in a significant decease in pressure-dependent myogenic contractions. Inhibition of eNOS with N G -nitro- l -arginine did not alter the myogenic response in either saline control or cocaine-treated animals. In females, cocaine caused a significant increase in pressure-dependent myogenic contractions. N G -nitro- l -arginine did not affect the myogenic response in the control animals but blocked the cocaine-mediated effect. In both males and females, the pressure-induced increases in vessel wall Ca 2+ concentrations were not significantly different between cocaine and saline groups. The ratio of changes in the diameter to Ca 2+ concentrations in the pressurized arteries was significantly less in male but greater in female offspring after cocaine treatment. The results suggest that prenatal cocaine exposure causes reprogramming of coronary myogenic tone via changes in the Ca 2+ sensitivity in a sex-dependent manner, leading to an increased risk of dysfunction of coronary autoregulation in adult offspring.

Epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of cardiovascular diseases and hypertension in adult life. The present study tested the hypothesis that prenatal cocaine exposure causes reprogramming of vascular reactivity, leading to an increased risk of hypertension in adult offspring. Pregnant rats received cocaine (30 mg kg −1 day −1 ) or saline from days 15 to 21 of gestational age, and experiments were conducted in 3-month-old offspring. Cocaine had no effect on the baseline blood pressure but significantly increased norepinephrine-stimulated blood pressure and decreased the baroreflex sensitivity in male but not female offspring. The cocaine treatment significantly increased norepinephrine-induced contractions in pressurized resistance–sized mesenteric arteries but not in aortas, which was primarily because of a loss of endothelial NO synthase–mediated inhibition and an enhanced Ca 2+ sensitivity in mesenteric arteries. In addition, the cocaine treatment significantly attenuated the endothelium-dependent relaxation in mesenteric arteries in male but not female offspring. Endothelial NO synthase protein levels in aortas but not mesenteric arteries were significantly increased in the cocaine-treated animals. However, cocaine significantly decreased phosphorylation levels of endothelial NO synthase in both aortas and mesenteric arteries. The results suggest that prenatal cocaine exposure programs vascular contractility via changes in endothelial NO synthase–regulated Ca 2+ sensitivity of myofilaments in the sex- and tissue-dependent manners in resistance arteries leading to an increased risk of hypertension in male offspring.

In the present study we tested the hypothesis that prenatal nicotine exposure increases heart susceptibility to ischemia/reperfusion (I/R) injury in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout gestation. Nicotine treatment resulted in a rapid and transient decrease in food-intake and a moderate decrease in maternal body weight gain. Hearts were isolated from adult male and female offspring and subjected to I/R in a Langendorff preparation. Nicotine significantly attenuated left ventricle (LV) developed pressure, heart rate, and coronary flow rate in female but not male hearts at baseline. Additionally, nicotine significantly increased LV infarct size and attenuated postischemic recovery of LV function in both male and female offspring with more pronounced effects in females. In female but not male hearts, nicotine significantly decreased the postischemic coronary flow rate. However, coronary nitric oxide release was decreased in male but not female hearts. Caspase-3, -8, and -9 levels were not significantly changed in either female or male hearts. However, nicotine caused a significant decrease in protein levels of protein kinase (PK) Cepsilon in both male and female hearts and a decrease in PKCdelta levels in female hearts only. Control studies of maternal food restriction showed that a moderate decrease in maternal body weight gain had no effect on female hearts but significantly improved postischemic recovery of LV function in male hearts. The results suggest that prenatal nicotine exposure causes in utero programming of the PKC isozyme gene expression pattern in the developing heart and increases heart susceptibility to I/R injury in adult offspring.

Recent studies indicate that smoking/nicotine increases maternal blood pressure and decrease in uterine blood flow in pregnancy. However, the mechanisms are not fully understood. The present study was designed to test the hypothesis that nicotine exposure decreases endothelium-dependent relaxation and increases vascular contractility of the uterine artery in pregnancy. Uterine arteries were isolated from near-term ( approximately 140 days gestation) pregnant ewes. Arteries were subjected to acute (20 min) or chronic (48 h) nicotine treatment, and agonist-induced contractions and relaxations were measured in tissue bath. Endothelial eNOS was detected by immunohistochemistry in situ in arteries and by Western blotting in isolated endothelial cells. Chronic nicotine treatment produced a concentration-dependent increase in alpha(1)-adrenoceptor agonist phenylephrine-induced contractions. In contrast, the acute treatment showed no effect. Inhibition of eNOS with N(G)-nitro-L-arginine (L-NNA) significantly increased phenylephrine-induced contractions, which was abolished in uterine arteries after chronic nicotine treatment. In the presence of L-NNA, there was no significant difference in phenylephrine-induced contractions between control and nicotine-treated vessels. Chronic, but not acute, nicotine treatment significantly attenuated the calcium ionophore A23187-induced relaxations. Unlike A23187, the endothelium-independent relaxation mediated by sodium nitroprusside was not affected by nicotine. Endothelial eNOS protein levels and the phosphorylation levels of eNOS(Ser1179) were significantly decreased in nicotine-treated uterine arteries. The results suggest that nicotine impairs uterine vascular function in pregnancy, which may lead to an increased vascular resistance and a decrease in uterine blood flow.

Background Serum a-fetoprotein (AFP) is one of the most common diagnostic markers for hepatocellular cancer (HCC) in the laboratory. As other immunoassays, AFP determination is not free from interferences. Natural antibodies like rheumatoid factors (RFs) may induce falsely elevated results, leading to misdiagnosis and expensive unnecessary explorations. Methods Serum samples containing AFP were spiked with moderate- or high-concentration RFs, and samples with high RF levels were spiked with AFP. The original sera, as well as the mixtures were tested for AFP by one-step and two-step sandwich ELISA. Results In the spiked specimens, addition of RFs caused significant bias in the measurement of AFP. The threshold for triggering significant interference was 260 IU/mL for RFs and 74 ng/mL for AFP. Conclusions In studies on the prevalence and clinical significance of serum AFP, RF interference should be considered and RF testing should be performed.

Human epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of ischemic heart disease in later adult life. Although adult lifestyle adds to the effects developed during intrauterine life, compelling evidence indicates that the association of ischemic heart disease with adverse intrauterine environment does not reflect confounding variables linked to adult lifestyle. It is suggested that epigenetic programming in the gene expression pattern caused by adverse intrauterine environments at a critical period of development in early life plays an important role in the heart development, and its lifelong pathophysiological consequences in the adult heart. Potential fetal programming of adult disease has been shown in maternal undernutrition and fetal exposure to glucocorticoids, hypoxia, alcohol, tobacco smoking, and cocaine. Although early epidemiological studies suggest that small body size at birth is associated with an increased risk of death from ischemic heart disease in the adult, it is becoming clear that fetal growth restriction is not a prerequisite of adult disease. Recent animal studies suggest that adverse intrauterine environments suppress fetal cardiac function, alter cardiac gene expression pattern, increase apoptosis of cardiomyocytes, cause a premature exit of the cell cycle of cardiomyocytes and myocyte hypertrophy, and result in an increase in susceptibility of the adult heart to ischemia-reperfusion injury. This review discusses recent epidemiological evidence in humans, as well as evidence from studies in experimental animals, of an association of adverse intrauterine environments and an increased risk of ischemic heart disease in the adult, and the possible molecular mechanisms of epigenetic programming involved in fetal gene expression pattern, which is essential in explaining many fundamental biological processes by which a variety of cardiovascular dysfunctions and disease emerge and evolve.

Cocaine decreases coronary artery endothelial-dependent vasorelaxation. To explore the potential mechanisms, the present study examined the effect of cocaine on nitric oxide release in bovine coronary artery endothelial cells (BCAECs). In the absence of cocaine, basal nitric oxide release from BCAECs continued to accumulate in the medium over the period from 6 to 72 h. Cocaine significantly decreased nitric oxide release at each time point of the study. At 48-h treatment, cocaine (3-30 muM) produced a concentration-dependent decrease in nitric oxide release in BCAECs. In accordance with its inhibition of nitric oxide release, cocaine decreased endothelial nitric-oxide synthase (eNOS) protein levels in BCAECs in a concentration-dependent manner. In addition to the prolonged effect, cocaine pretreatment for 1 h significantly decreased basal and ATP-induced nitric oxide release in BCAECs. Whereas acute cocaine treatment did not affect basal levels of free intracellular calcium concentrations in BCAECs, it significantly decreased the ATP-induced elevation of intracellular calcium and increased its time lag to reach the peak. A quantitative approach by immunofluorescence microscopy revealed that cocaine significantly increased eNOS localized at the cell membrane in BCAECs. Collectively, the results suggest that cocaine inhibits nitric oxide release in BCAECs by decreasing intracellular calcium mobilization, increasing the inactive state of eNOS, and decreasing eNOS protein levels.

Corticosteroid hormones play an important role in the control of vascular smooth muscle tone by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. Increased cortisol response has been associated with an increase in arterial contractile sensitivity to norepinephrine and vascular resistance. Glucocorticoids regulate vascular reactivity by acting on both endothelial and vascular smooth muscle cells. Both glucocorticoid receptor protein and mRNA have been identified in endothelial and vascular smooth muscle cells. In endothelial cells. glucocorticoids suppress the production of vasodilators. such as prostacyclin and nitric oxide. In vascular smooth muscle cells. glucocorticoids enhance agonist-mediated pharmacomechanical coupling at multiple levels. The effect of glucocorticoids on vascular reactivity is regulated by 11 beta-hydroxysteroid dehydrogenase (11beta-SD). The presence of 11beta-HSD in many tissues suggests that it modulates the access of corticosteroids to their receptors at both renal and extra-renal sites. The two 11beta-HSD isozymes catalyze the interconversion of cortisol and cortisone. Type 11beta-HSD has bidirectional activity, while the type 2 mainly converts cortisol into cortisone, the biologically inactive form. Both type 1 and type 2 11beta-HSD have been found in vascular endothelial and smooth muscle cells, suggesting that abnormal 11B-HSD expression may play a pathogenic role in the common forms of hypertension. In this article, we review possible mechanisms involved in the glucocorticoid-mediated potentiation of vascular reactivity, its regulation by 11beta-HSD, and their physiological and pathophysiological significance.

Background and Purpose— Maternal cigarette smoking increases the risk of neonatal morbidity. We tested the hypothesis that perinatal nicotine exposure causes heightened brain vulnerability to hypoxic–ischemic (HI) injury in neonatal rats through aberrant expression patterns of angiotensin II type 1 (AT 1 R) and type 2 (AT 2 R) receptors in the developing brain. Methods— Nicotine was administered to pregnant rats through subcutaneous osmotic minipumps. HI brain injury was determined in 10-day-old pups. AT 1 R and AT 2 R expression patterns were assessed through Western blotting, quantitative polymerase chain reaction, immunofluorescence, and confocal imaging. Results— Perinatal nicotine exposure significantly increased HI brain infarct size in male, but not female, pups. In fetal brains, nicotine caused a decrease in mRNA and protein abundance of AT 2 R but not AT 1 R. The downregulation of AT 2 R persisted in brains of male pups, and nicotine treatment resulted in a significant increase in methylation of CpG locus 3 bases upstream of TATA-box at the AT 2 R gene promoter. In female brains, there was an increase in AT 2 R but a decrease in AT 1 R expression. Both AT 1 R and AT 2 R expressed in neurons but not in astrocytes in the cortex and hippocampus. Central application of AT 1 R antagonist losartan or AT 2 R antagonist PD123319 increased HI brain infarct size in both male and female pups. In male pups, AT 2 R agonist CGP42112 abrogated nicotine-induced increase in HI brain infarction. In females, PD123319 uncovered the nicotine's effect on HI brain infarction. Conclusion— Perinatal nicotine exposure causes epigenetic repression of the AT 2 R gene in the developing brain resulting in heightened brain vulnerability to HI injury in neonatal male rats in a sex-dependent manner.

Circular, variable, broad-bandpass filters with induced transmission (CV-IT-BF) at 200-1100 nm are introduced and their advantages are described. Designs are also presented of CV-IT-BF's for regions of 200-400, 400-700, 700-1100 nm, as well as regularities of the matching coefficients of circular, wedge-shaped matching layers and of the physical thickness of metallic circular, wedge-shaped layers, both of which continuously vary linearly with the wavelengths. Finally, parameter analyses of typical designs of the CV-IT-BF are described together with experimental demonstrations and examples of applications.

Epidemiological studies suggest that maternal cigarette smoking is associated with an increased risk of elevated blood pressure (BP) in postnatal life. The present study tested the hypothesis that prenatal nicotine exposure causes an increase in BP response to angiotensin II (Ang II) in adult offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. BP and vascular responses to Ang II were measured in 5-month–old adult offspring. Prenatal nicotine had no effect on baseline BP but significantly increased Ang II–stimulated BP in male but not female offspring. The baroreflex sensitivity was significantly decreased in both male and female offspring. Prenatal nicotine significantly increased arterial media thickness in male but not female offspring. In male offspring, nicotine exposure significantly increased Ang II–induced contractions of aortas and mesenteric arteries. These responses were not affected by inhibition of endothelial NO synthase activity. Losartan blocked Ang II–induced contractions in both control and nicotine-treated animals. In contrast, PD123319 had no effect on Ang II–induced contractions in control but inhibited them in nicotine-treated animals. Nicotine significantly increased Ang II type 1 receptor but decreased Ang II type 2 receptor protein levels, resulting in a significant increase in the ratio of Ang II type 1 receptor/Ang II type 2 receptor in the aorta. Furthermore, the increased contractions of mesenteric arteries were mediated by increases in intracellular Ca 2+ concentrations and Ca 2+ sensitivity. These results suggest that prenatal nicotine exposure alters vascular function via changes in Ang II receptor–mediated signaling pathways in adult offspring in a gender-specific manner, which may lead to an increased risk of hypertension in male offspring.

Maternal cigarette smoking is the single most widespread prenatal insult. Smoking has long been associated with adverse pregnancy outcomes, both for the mother, her fetus, and newborn. The present ...