I-level positive airway pressure ventilation for patients with hypoxemia after coronary artery bypass grafting.

Coronary artery bypass grafting (CABG) is an effective scheme for treatment of myocardial ischemia. Hypoxemia is a common complication of CABG, which can affect surgical effect and prognosis and even induce multiple organ failure. To explore the clinical efficacy of bi-level positive airway pressure ventilation in the treatment of CABG-associated hypoxemia, 216 patients who were admitted to our hospital between August 2015 and April 2017 and developed CABG-associated hypoxemia were selected and randomly divided into 2 groups, an observation group (n=108) and a control group (n=108). Patients in the control group were given conventional treatment including continuous oxygen inhalation through nasal tube, anti-infection, bronchodilation, phlegm resolving, nutrition support, analgesia, cardiac function maintenance, coronary dilatation, anticoagulation and maintenance of stable internal environment, while patients in the observation group were given positive airway pressure ventilation via a breathing machine or nasal mask besides the conventional treatment.

An SSLP marker-anchored BAC framework map of the mouse genome.

We have constructed a BAC framework map of the mouse genome consisting of 2,808 PCR-confirmed BAC clusters, using a previously described method. Fingerprints of BACs from selected clusters confirm the accuracy of the map. Combined with BAC fingerprint data, the framework map covers 37% of the mouse genome.

Engineering a mouse balancer chromosome.

Balancer chromosomes are genetic reagents that are used in Drosophila melanogaster for stock maintenance and mutagenesis screens. Despite their utility, balancer chromosomes are rarely used in mice because they are difficult to generate using conventional methods. Here we describe the engineering of a mouse balancer chromosome with the Cre-loxP recombination system. The chromosome features a 24-centiMorgan (cM) inversion between Trp53 (also known as p53) and Wnt3 on mouse chromosome 11 that is recessive lethal and dominantly marked with a K14-Agouti transgene. When allelic to a wild-type chromosome, the inversion suppresses crossing over in the inversion interval, accompanied by elevated recombination in the flanking regions. The inversion functions as a balancer chromosome because it can be used to maintain a lethal mutation in the inversion interval as a self-sustaining trans-heterozygous stock. This strategy can be used to generate similar genetic reagents throughout the mouse genome. Engineering of visibly marked inversions and deficiencies is an important step toward functional analyses of the mouse genome and will facilitate large-scale mutagenesis programs.

Micro-Raman spectroscopy of algae: composition analysis and fluorescence background behavior.

Preliminary feasibility studies were performed using Stokes Raman scattering for compositional analysis of algae. Two algal species, Chlorella sorokiniana (UTEX #1230) and Neochloris oleoabundans (UTEX #1185), were chosen for this study. Both species were considered to be candidates for biofuel production. Raman signals due to storage lipids (specifically triglycerides) were clearly identified in the nitrogen-starved C. sorokiniana and N. oleoabundans, but not in their healthy counterparts. On the other hand, signals resulting from the carotenoids were found to be present in all of the samples. Composition mapping was conducted in which Raman spectra were acquired from a dense sequence of locations over a small region of interest. The spectra obtained for the mapping images were filtered for the wavelengths of characteristic peaks that correspond to components of interest (i.e., triglyceride or carotenoid). The locations of the components of interest could be identified by the high intensity areas in the composition maps. Finally, the time evolution of fluorescence background was observed while acquiring Raman signals from the algae. The time dependence of fluorescence background is characterized by a general power law decay interrupted by sudden high intensity fluorescence events. The decreasing trend is likely a result of photo-bleaching of cell pigments due to prolonged intense laser exposure, while the sudden high intensity fluorescence events are not understood.

MiR-201-5p alleviates lipopolysaccharide-induced renal cell dysfunction by targeting NOTCH3.

OBJECTIVE: Lipopolysaccharide (LPS)-induced inflammation and dysfunction in the kidney may be the major risk factors for subsequent acute kidney injury (AKI). Previous studies have reported that up-regulation of notch receptor 3 (NOTCH3) expression is accompanied with renal epithelium and podocyte damage. Herein, we aimed to investigate whether NOTCH3 was involved in lipopolysaccharide (LPS)-induced AKI and renal cell dysfunction. MATERIALS AND METHODS: Septic mice were established using LPS (20 mg/kg) intraperitoneally. mRNA and protein expression in the kidney and renal cell was performed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Cell counting kit-8 (CCK8) and flow cytometry were used to measure cell viability and apoptosis, respectively. Bioinformatics algorithm and Luciferase reporter gene assay were performed to validate whether NOTCH3 was a direct target of miR-201-5p. RESULTS: Up-regulation of NOTCH3 and down-regulation of miR-201-5p were observed in the kidney of LPS-induced septic mice. LPS-stimulated TCMK-1 and MPC5 cells led to an increase in NOTCH3 and a decrease in miR-201-5p expression levels. Bioinformatics algorithm and experimental measurements validated that NOTCH3 was a direct target of miR-201-5p. Overexpression of miR-201-5p protected against LPS-induced renal cell growth inhibition, apoptosis and inflammatory response via the suppression of toll-like receptor 4 (TLR4)/NOTCH3 signaling pathway. CONCLUSIONS: The novel role of miR-201-5p via the inhibition of LPS-activated TLR4/NOTCH3 might provide a potential therapeutic strategy for the treatment of LPS-induced AKI.

10p11.2 to 10q11.2 is a yet unreported region leading to unbalanced chromosomal abnormalities without phenotypic consequences.

Directly transmitted unbalanced chromosomal abnormalities (UBCA) or euchromatic variants (EV) were recently reported for >50 euchromatic regions of almost all human autosomes. UBCA and EV are comprised of a few megabases of DNA, and carriers are in many cases clinically healthy. Here we report on partial trisomies of chromosome 10 within the pericentromeric region which were detected by standard G banding. Those were referred for further delineation of the size of these duplicated regions for molecular cytogenetics and/or array-CGH. Partial trisomies of chromosome 10 in the pericentromeric region were identified prenatally in seven cases. A maximum of three copies of the region from 10p12.1 to 10q11.22 was observed in all cases without apparent clinical abnormalities. The imbalances were either caused by a direct duplication in one familial case or by de novo small supernumerary marker chromosomes (sSMC). Thus, we report a yet unrecognized chromosomal region subject to UBCA detected in seven unrelated cases. To the best of our knowledge, this is the first report of a UBCA in the pericentromeric region of chromosome 10 that is not correlated with any clinical consequences.

Identification of critical regions for clinical features of distal 10q deletion syndrome.

Array comparative genomic hybridization studies were performed to further characterize cytogenetic abnormalities found originally by karyotype and fluorescence in situ hybridization in five clinical cases of distal 10q deletions, including several with complex cytogenetic rearrangements and one with a partial male-to-female sex-reversal phenotype. These results have enabled us to narrow the previously proposed critical regions for the craniofacial, urogenital, and neuropsychiatric disease-related manifestations associated with distal 10q deletion syndrome. Furthermore, we propose that haploinsufficiency of the DOCK1 gene may play a crucial role in the pathogenesis of the 10q deletion syndrome. We hypothesize that alteration of DOCK1 and/or other genes involved in regulation and signaling of multiple pathways can explain the wide range of phenotypic variability between patients with similar or identical cytogenetic abnormalities.

Functional roles of exosomes in cardiovascular disorders: a systematic review.

Cardiovascular diseases are major causes of people death associated with high mortality and disability. Exosomes are nanosized extracellular vesicles containing protein, lipid, transcription factors, mRNAs, non-coding RNA (ncRNA) and nucleic acid contents, which are critical players of intercellular communication via long-range signals or cell-to-cell contact. The emergence of exosomes provides favorable strategies for the diagnosis and treatment of cardiovascular diseases. Exosomes-based molecular mechanisms are important for developing novel therapeutic approaches for cardiovascular events. In this review, we will (1) provide insights into the detrimental and beneficial effects of exosomes on cardiovascular physiology, (2) summarize the underlying biological mechanisms of the exosome in cardiovascular events, (3) investigate the therapeutic value of exosomes for cardiovascular disorders.

Array-based comparative genomic hybridization and copy number variation in cancer research.

Array-based comparative genomic hybridization (aCGH) is a molecular cytogenetic technique used in detecting and mapping DNA copy number alterations. aCGH is able to interrogate the entire genome at a previously unattainable, high resolution and has directly led to the recent appreciation of a novel class of genomic variation: copy number variation (CNV) in mammalian genomes. All forms of DNA variation/polymorphism are important for studying the basis of phenotypic diversity among individuals. CNV research is still at its infancy, requiring careful collation and annotation of accumulating CNV data that will undoubtedly be useful for accurate interpretation of genomic imbalances identified during cancer research.

Association of the common cold in the first trimester of pregnancy with birth defects.

OBJECTIVE: To examine the association between the common cold with or without fever in the first 3 months of pregnancy and birth defects in offspring. DESIGN: A case-control study. SETTING: Data are from the Shanghai Birth Defects Monitoring Program, conducted in 29 hospitals in Shanghai, China from October 1, 1986 to September 30, 1987. SUBJECTS: A total of 986 birth defects cases, 990 frequency-matched live birth controls, and 159 stillbirth controls. RESULTS: Modestly elevated risk of birth defects was identified among women who reported having a cold with or without fever in the first trimester of pregnancy. Notably increased relative risks were observed for anencephalus (odds ratio [OR] = 3.9, 95% confidence interval [CI] = 2.0 to 7.7), spina bifida (OR = 4.1, 95% CI = 1.7 to 9.7), hydrocephalus (OR = 2.3, 95% CI = 1.1 to 5.1), cleft lip (OR = 2.2, 95% CI = 1.4 to 3.4), and undescended testicle (OR = 1.8, 95% CI = 1.0 to 3.0). Our study further found that the overall relative risks were consistent by using two different control groups, suggesting that this association was unlikely to be due to recall or report bias. CONCLUSION: Common cold in the first trimester of pregnancy may be associated with an increased risk of birth defects in offspring. However, these findings should be interpreted cautiously.

Perinatal mortality in Shanghai: 1986-1987.

The incidence of, and risk factors associated with, perinatal mortality in Shanghai during 1986-1987 are examined using data from a multi-site study conducted in 29 hospitals. The overall perinatal mortality rate was 14.96 per 1000 births. The mortality rates of antepartum fetal death, intrapartum fetal death and early neonatal death were 5.97, 2.06 and 6.94 per 1000 births, respectively. The perinatal mortality rates increased in winter and late spring. Male neonates were 1.5 times more likely to die than females. Low birthweight and preterm infants had 15 to 80 times higher risk of perinatal death. Higher parity, multiple pregnancy, and maternal age greater than or equal to 35 years were the risk factors for perinatal mortality. Asphyxia, cord complications, and congenital malformations were found to be the major causes of perinatal deaths. Comparison of mortality rates between Shanghai and the US suggests that the shortage of advanced technology in perinatal care (e.g. neonatal intensive care units) is a major obstacle to the reduction of perinatal mortality in Shanghai.

PIP: Although Shanghai's perinatal mortality rate (PMR) approximates that found in some developed countries, this rate has remained stationary at about 13/1000 births for the past decade. To document the incidence of perinatal mortality and identify factors inhibiting further declines in the PMR, data were collected on perinatal deaths occurring in 1986-87 in a sample of 29 randomly selected hospitals in the Shanghai Municipality. In the 12-month monitoring period, there were 75,756 births (accounting for 40% of total births in the Municipality) and 1134 perinatal deaths, for a PMR of 14.96/1000. This figure included 452 antepartum deaths (5.97/1000), 156 intrapartum deaths (2.06/1000), and 526 early neonatal deaths (6.94/1000). Antepartum and intrapartum deaths were largely attributable to cord complications, intrapartum asphyxia, congenital malformation, and placental causes, while early neonatal deaths tended to result from asphyxia, congenital malformation, and intracranial hemorrhage. The major risk factors for perinatal mortality were birthweight under 2500 grams and prematurity. The PMRs were 678.0 and 108.5 for the 1000-1499 gram birthweight categories, respectively, compared to 8.1 for newborns weighing 2500-3999 grams, and 137.7 for the 28-26 week gestational age group compared to 9.2 for infants delivered at 37-41 weeks. An increased risk of mortality was also associated with parity over 2, multiple births, and maternal age 35 years and over. For normal birthweight and full-term infants, the PMRs recorded in this study approximated those found in the US. However, a preterm infant has a 4-fold greater risk of early neonatal death in Shanghai than the US, suggesting that a shortage of high-technology perinatal care if the major factor inhibiting further reductions in Shanghai's PMR.

A case-control study of paternal smoking and birth defects.

Although the influence of paternal smoking on birth defects is of great public interest, epidemiological evidence concerning this potential relationship is extremely limited. A stratified random sample of 29 hospitals in the Shanghai Municipality, China, was used to select 1012 birth defects cases and controls. Mothers of the cases and controls were interviewed in the hospitals from October 1986 to September 1987. A modest relationship between paternal smoking and overall birth defects in offspring was identified [odds ratio (OR) = 1.21, 95% confidence interval (CI): 1.01-1.45]. More markedly elevated risks were identified for anencephalus (OR = 2.1), spina bifida (OR = 1.9), pigmentary anomalies of the skin (OR = 3.3) and varus/valgus deformities of the feet (OR = 1.8). Our analysis also shows that paternal smoking is more likely to be associated with multiple rather than isolated malformations. A paternally-mediated effect of smoking on birth defects is suggested and further studies are encouraged.

PIP: The effect of paternal smoking on birth defects was examined using data from the Shanghai Birth Defects Monitoring Program in Shanghai Municipality from October 1986 to September 1987. A stratified random sample of 29 hospitals was selected. A total of 75,756 births with weights of 1000 gm or over were recorded. The final sample included 1012 cases and 1012 controls without adjustment for confounding factors. Maternal exposure to radiation, chemicals, and pesticides during pregnancy and the smoking and alcohol consumption habit of the husband were recorded. The relative risk (RR) of birth defects associated with paternal smoking was 1.2. Paternal smoking was associated with a 2.1- fold increase of anencephalus; infants whose fathers smoked were 3.3 times as likely to have had pigmentary anomalies of the skin, and 2.3 times as likely to have a diaphragmatic hernia. The odds ratio (OR) of spina bifida was 1.9 and varus or valgus deformities of feet had an OR of 1.8. The OR of these anomalies was also over 1.5: eye anomalies, microtia or absence of ear, nasal bone absence, cleft palate without cleft lip, brachydactylia or adactylia, undescended testicle, and polycystic kidney. The possible dose-response relationship between paternal smoking and birth defects was assessed in 3 groups: 1-9, 10- 19, and 20 or more cigarettes per day. Similar increased RRs across smoking levels were found for anencephalus, cleft palate, and pigmentary anomalies of the skin. Increasing risk among the heavier smokers was apparent for spina bifida, nasal bone absence, varus or valgus deformities of the feet, and diaphragmatic hernia. Paternal smoking was slightly more related to multiple defects than to single defects. This suggests a modest link between paternal smoking and total birth defects and a stronger effect of paternal smoking and anencephalus and spina bifida risk, consistent with a previous study.

Risk factors associated with antepartum fetal death.

This study examined risk factors that contribute to antepartum fetal death. The population-based sample included 416 antepartum fetal deaths and 449 normal births as controls, from 29 hospitals in Shanghai, China. In addition to small-for-gestational-age and severe pregnancy-induced hypertension, exposure to environmental hazards (radiation, chemicals and pesticides) was significantly associated with fetal death. Elevated relative risk of fetal death was also found in pregnant women whose husbands smoked (adjusted odds ratio = 1.4). Clinicopathologic evidence further confirmed that exposure to hazards, especially in the first trimester, increased the risks of congenital anomalies (odds ratio = 2.7) and antepartum fetal death from congenital malformations (odds ratio = 3.5). This study also showed that threatened abortion was a significant predictor of risk of fetal death. No significant relationships were identified between sex of fetus, mild or moderate pregnancy-induced hypertension, maternal anemia and antepartum fetal death.

[Multivariate analysis of relationship between breast feeding and infant physical development].

Longitudinal analysis with generalized estimating equation (GEE) revealed breast feeding can promote infant physical development and growth, and cross-sectional analysis with canonical correlation showed protein intake with breast milk as its main source brought about infants to develop physically tall and lean at first, which might support the theory that protein intake affects more on their development and growth. The extent of infant physical development and growth varied with the amount of breast milk of his or her mother, which should be caught attention in comparison of infant physical development with different feeding patterns. It is suggested that intervention of breast feeding should be implemented during perinatal period and 1-2 months after delivery with emphasis on health education.

Role of stromal-derived factor-1/CXCR4 in neo-intimal repair.

Neo-intimal hyperplasia is one of the major causes of restenosis in which stromal cell-derived factor-1 (SDF-1α) and its receptor CXCR4 play an important role. In a rat common carotid artery balloon injury model, the number of CD34(+)CXCR4(+) cells was significantly increased immediately after injury (p < 0.01), followed by a gradual decrease to baseline seven days after the injury. Furthermore, the plasma (SDF-1α) level was markedly elevated, and peaked 24 hours after injury (p < 0.01), followed by a rapid decrease to baseline level seven days after the injury. In the injured common carotid artery, the mRNA expression of (SDF-1α) was elevated immediately after injury, followed by a gradual decline, but that of CXCR4 was increased four days after injury. Immuno-histochemistry displayed CXCR4-positive staining one day after injury, which then gradually increased and continued for at least one month. In addition, administration of AMD3100 (200 ng/kg, i.p.), a CXCR4 antagonist, did not affect the number of CD34(+)CXCR4(+) cells, the elevated level of plasma (SDF-1α) and expression of (SDF-1α) mRNA. The expression of CXCR4 mRNA and protein however was markedly decreased, and detectable CXCR4-positive cells occurred four days after injury, followed by a decreased intensity of staining. We also found that, three months after balloon injury, stenosis of the carotid artery intima in the group that received AMD3100 was significantly less than in the untreated group (p < 0.05). Therefore, (SDF-1α)/CXCR4 played a crucial role in the intimal hyperplasia, and restenosis may have be attenuated after inhibition of CD34(+)CXCR4(+) cells in the intima.

An HDAC1-binding domain within FATS bridges p21 turnover to radiation-induced tumorigenesis.

There is a gap between the initial formation of cells carrying radiation-induced genetic damage and their contribution to cancer development. Herein, we reveal a previously uncharacterized gene FATS through a genome-wide approach and demonstrate its essential role in regulating the abundance of p21 in surveillance of genome integrity. A large exon coding the NH2-terminal domain of FATS, deleted in spontaneous mouse lymphomas, is much more frequently deleted in radiation-induced mouse lymphomas. Its human counterpart is a fragile site gene at a previously identified loss of heterozygosity site. FATS is essential for maintaining steady-state level of p21 protein and sustaining DNA damage checkpoint. Furthermore, the NH2-terminal FATS physically interacts with histone deacetylase 1 (HDAC1) to enhance the acetylation of endogenous p21, leading to the stabilization of p21. Our results reveal a molecular linkage between p21 abundance and radiation-induced carcinogenesis.

Congenital diaphragmatic hernia associated with duplication of 11q23-qter.

Congenital diaphragmatic hernia (CDH) is a relatively common birth defect with a high mortality. Although little is known about its etiology, there is increasing evidence for a strong genetic contribution. Both numerical and structural chromosomal abnormalities have been described in patients with CDH. Partial trisomy 11q and partial trisomy 22 associated with the common t(11;22) has been reported in several cases of CDH. It has been assumed that the diaphragmatic defect seen in these individuals was primarily due to duplication of material from chromosome 22q11. However, in this report we describe a family with a t(11;12) in which one of two brothers with partial trisomy 11q has a left sided posterolateral CDH. This is the second case of CDH in partial trisomy 11q due to an unbalanced translocation other than t(11;22). Using array-based comparative genomic hybridization and fluorescent in situ hybridization, we mapped the breakpoints in both brothers and their mother who is a balanced translocation carrier. Our results suggest that duplication of one or more genes on a approximately 19 Mb region of 11q23.3-qter predisposes to the development of CDH. These effects may be the primary cause of CDH in individuals t(11;22) or may be additive to effects from the duplication of chromosome 22 material. We also conclude that the partial trisomy 11q syndrome has a variable phenotype and that CDH should be added to the spectrum of anomalies that can be present in this syndrome.

Severe vomiting during pregnancy: antenatal correlates and fetal outcomes.

Neither the cause nor the effect of severe vomiting during pregnancy is well understood. This study examines possible causes of severe vomiting and associations between this disorder and fetal outcomes. One thousand eight hundred sixty-seven women with normal singleton live births were included in the analysis. The cumulative incidence of severe vomiting during pregnancy was 10.8%. Women with chronic liver disease had a threefold increased risk of severe vomiting during pregnancy. Paternal smoking was associated with a twofold increased risk of maternal vomiting. A modest association between severe vomiting and fetal growth retardation was identified (OR = 1.4, 95% CI: 0.9-2.3). Severe vomiting was also found to be associated with preeclampsia (OR = 1.5, 95% CI: 1.0-2.4). Our study indicates that passive smoking is a risk factor for vomiting during pregnancy, which may, in turn, increase the risk of fetal growth retardation.

Birth defects in relation to threatened abortion.

The evidence for the association between threatened abortion and birth defects is limited and inconsistent. This study examined this relation using data from the Shanghai Birth Defects Monitoring Program. A total of 1,013 cases of birth defects and an equal number of controls were analyzed. Our study showed that women with threatened abortion had a 50% higher risk of having a baby with birth defects compared with those without this complication, controlling for other factors (adjusted odds ratio = 1.5; 95% confidence interval = 1.1-2.1). Threatened abortion was generally related to defects of the urogenital system, heart and circulatory system, and musculoskeleton and limbs and was specifically associated with polydactyly, undescended testicle, and hypospadias.

Pregnancy-induced hypertension and early neonatal death: a case-control study.

Literature on the association between pregnancy-induced hypertension and early neonatal death is limited. The present case-control study consisted of 342 early neonatal deaths and 523 frequency-matched controls. After controlling for other factors such as infant sex, gravidity, maternal age, threatened abortion, and maternal anemia, moderate to severe pregnancy-induced hypertension was associated with an increased risk of early neonatal death with apparent dose-effect gradients (odds ratio = 1.8 for moderate and 2.2 for severe). The biologic plausibility of pregnancy-induced hypertension as a cause of neonatal mortality is discussed.