On the origin of cardiac mucosa： A histological and immunohistocheroical study of cytokeratin expression patterns in the developing esophagogastric junction region and stomach

AIM To examine the fetal and neonatal esophagogastric junction region (EGJ) histologically for the presence of an equivalent to adult cardiac mucosa (CM); to study the expression patterns of all cytokeratins (CK) relevant to the EGJ during gestation; to compare the CK profile of the gestational and the adult EGJ; and to determine the degree of development in the adult EGJ histology and CK profile during gestation. METHODS: Forty-eight fetal autopsy specimens of the EGJ were step-sectioned and stained with hematoxylin and eosin (H&E) to select sections showing the mucosal lining. Immunohistochemistry for CK5, 7, 8, 13, 18, 19, and 20 was performed. Antibody staining was then graded for location, intensity, and degree. RESULTS: The distal esophagus was lined by simple columnar epithelium from 12-wk gestational age (GA). The proximal part of this segment consisted of mucusproducing epithelium, devoid of parietal cells. CK5 and 13 were present exclusively in multilayered epithelia and CK8, 18, and 19 predominantly in simple columnar epithelium. There were no differences in the frequencies of the coordinate CK7+/20+ and the CK7-/20-immunophenotypes between different locations. The prevalence of the CK7+/20-immunophenotype decreased, and that of the CK7-/ 20+ immunophenotype increased significantly from the distal esophagus to the distal stomach. CONCLUSION: Fetal columnar-lined lower esophagus (fetal CLE) may be the equivalent and precursor of the short segments of columnar epithelium found in the distal esophagus of some normal adult subjects. Esophageal simple columnar epithelium without parietal cells (ESN) may be the precursor of adult CM. The similarities between the fetal and adult EGJ and stomach CK expression patterns support the conclusion that adult CM has an identifiable precursor in the fetus. This would then indicate that at least a part of the adult CM has a congenital origin.     

Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues

AIM： To assess whether trace metal concentrations （which influence metabolism as both essential and non-essential elements） are increased or decreased in cancerous tissues and to understand the precise role of these metals in carcinogenesis.
METHODS： Concentrations of trace metals including Cd, Ni, Cu, Zn, Fe, Mg and Ca in both cancerous and noncancerous stomach tissue samples were determined by atomic absorption spectrometry （AAS）. Tissue samples were digested using microwave energy. Slotted tube atom trap was used to improve the sensitivity of copper and cadmium in flame AAS determinations.
RESULTS： From the obtained data in this study, the concentrations of nickel, copper and iron in the cancerous human stomach were found to be significantly higher than those in the non-cancerous tissues, by using t-test for the paired samples. Furthermore, the average calcium concentrations in the cancerous stomach tissue samples were found to be significantly lower than those in the non-cancerous stomach tissue samples by using t-test. Exceedingly high Zn concentrations （207-826 mg/ kg） were found in two paired stomach tissue samples from both cancerous and non-cancerous parts.
CONCLUSION： In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples.     

Tissue array for Tp53,C-myc,CCND1 gene over-expression in different tumors

AIM：To rapidly detect molecular alterations in different malignancies and investigate the possible role of Tp53,C-myc,and CCND1 genes in development of tumors in human organs and their adjacent normal tissues,as well as the possible relation between well-and poorly-differentiated tumors.METHODS：A tissue array consisting of seven different tumors was generated.The tissue array included 120 points of esophagus,120 points of stomach,80 points of rectum,60 points of thyroid gland,100 points of mammary gland,80 points of liver,and 80 points of colon.Expressions of Tp53,C-myc,and CCND1 were determined by RNA in situ hybridization.3＇ terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe were used.RESULTS：The expression level of Tp53 gene was higher in six different carcinoma tissue samples than in paracancerous tissue samples with the exception in colon carcinoma tissue samples（P 〈 0.05）.The expression level of CCND1 gene was significantly different in different carcinoma tissue samples with the exception in esophagus and colon carcinoma tissue samples.The expression level of C-myc gene was different in esophagus carcinoma tissue samples（c2 = 18.495,P = 0.000）,stomach carcinoma tissue samples（c2 = 23.750,P = 0.000）,and thyroid gland tissue samples（c2 = 10.999,P = 0.004）.The intensity of signals was also different in different carcinoma tissue samples and paracancerous tissue samples.CONCLUSION：Over-expression of the Tp53,CCND1,and C-myc genes appears to play a role in development of human cancer by regulating the expression of mRNA.Tp53,CCND1 and C-myc genes are significantly correlated with the development of different carcinomas.     

Hydrogen and methane gases are frequently detected in the stomach

AIM: To investigate the incidence of bacterial overgrowth in the stomach by using a new endoscopic method in which intragastric hydrogen and methane gases are collected and analyzed. METHODS: Studies were performed in 490 consecutive patients undergoing esophagogastroscopy. At endoscopy, we intubated the stomach without inflation by air, and 20 mL of intragastric gas was collected through the biopsy channel using a 30 mL syringe. Intragastric hydrogen and methane concentrations were immediately measured by gaschromatography. H pylori infection was also determined by serology. RESULTS: Most of intragastric hydrogen and methane levels were less than 15 ppm (parts per million). The median hydrogen and methane values (interquartile range) were 3 (1-8) ppm and 2 (1-5) ppm, respectively. The high hydrogen and methane levels for indication of fermentation were decided if the patient had the values more than 90 percentile range in each sample. When a patient had a high level of hydrogen or methane in one or more samples, the patient was considered to have fermentation. The overall incidence of intragastric fermentation was 15.4% (73/473). Intragastric methane levels were higher in the postoperative group than in other groups. None of the mean hydrogen or methane values was related to H pylori infection. CONCLUSION: Hydrogen and methane gases are more frequently detected in the stomach than expected, regardless of the presence of abdominal symptoms. Previous gastric surgery influences on the growth of methane-producing bacteria in the fasting stomach.     

Neuro-regulation of lower esophageal sphincter function as treatment for gastroesophageal reflux disease

The junction between the esophagus and the stomach is a specialized region, composed of lower esophageal sphincter （LES） and its adjacent anatomical structures, the gastric sling and crural diaphragm. Together these structures work in a coordinated manner to allow ingested food into the stomach while preventing reflux of gastric contents across the esophago-gastric junction （EGJ） into the esophagus. The same zone also permits retrograde passage of air and gastric contents into esophagus during belching and vomiting. The precise coordination required to execute such a complicated task is achieved by a finely-regulated high-pressure zone. This zone keeps the junction between esophagus and stomach continuously closed, but is still able to relax briefly via input from inhibitory neurons that are responsible for its innervation. Alterations of the structure and function of the EGJ and the LES may predispose to gastroesophageal reflux disease （GERD）.     

Nutritional status and quality of life of the gastric cancer patients in Changle County of China

AIM: To analyze the relation between nutrition and quality of life in the stomach cancer patients, evaluate the intake of daily nutrition of the patients, and study the feasibility of nutrition intervention in improving quality of life of the stomach cancer patients. METHODS: A total of 285 surgical stomach cancer patients reported in the Changle Cancer Registry from 2002 to 2003 were investigated with respect to their diet and quality of life. Daily nutrition intakes of the patients were calculated according to the Food Composition Database, and these data were compared with the reference values proposed by the Chinese Nutrition Society. The partial correlation was used to analyze the relationship between nutrition and quality of life in the patients. Stepwise multiple regression analyses were conducted to analyze the factors influencing nutrition intake in stomach cancer patients. RESULTS: Except vitamin C, there were statistical correlations between the nutrition and quality of life in stomach cancer patients, and differences of the daily nutrition intake among three groups (good, modest and bad quality of life) of the patients were significant. Most of the stomach cancer patients had a lower daily nutrition intake than the reference values. At the significance level α=0.05, the factors influencing the daily nutrition intake of the patients were number of meals a day, family income, way of operation, exercise and age. CONCLUSION: The nutritional status of the operated patients with stomach cancer may impact on their quality of life. The stomach cancer patients in Changle County have a low level of daily nutrition intake, which suggests that they have a bad nutritional status. To improve the quality of life of the patients, the nutrition intervention should be conducted. Increasing times of meals a day and having a high-protein, high-calorie foods can improve the nutritional status of the stomach cancer patients. Moreover, exercise for rehabilitation can whet the appetite of the patients and recover their body function, which in turn may improve the quality of life of the stomach cancer patients.     

Normothermic versus hypothermic fetal cardiopulmonary bypass with cardioplegic arrest on the feto-placental circulation

Background The requisite techniques for safe fetal cardiac arrest during cardiac interventions need to be further developed. Furthermore, little is known about the pathophysiologic effect of cardiopulmonary bypass(CPB)at different levels of temperature with cardioplegic arrest on the developing fetus. Methods Twelve pregnant goats were randomly divided into hypothermic CPB group(H group): cardiopulmonary bypass with perfusion at 30-32℃(n=6) and normothermic CPB group(N group): cardiopulmonary bypass with perfusion at 36℃-38℃(n=6). Fetal cardiopulmonary bypass was maintained including 30 minutes of cardiac arrest. Fetal mean arterial blood pressure(MAP) and heart rate(HR) were monitored. Fetal arterial blood samples were analyzed. The pulse index(PI) and resistance index(RI) of the fetal umbilical artery were recorded. Results The maternal weight,fetal weight and pump flow had no significant difference between the 2 groups. After clamp removal, two fetal hearts did not auto-beat in H group. The fetal HR and MAP b were significantly different(P0.05) etween the 2 groups. There was remarkable decreasing in post-CPB fetal HR and MAP in H group. A stable decrease in partial pressure of oxygen with a concomitant stable increase of carbon dioxide partial pressure in H group was noted.The lactic acid in H group was significantly higher than that in the N group(P0.05). The PI and RI in H group were significantly elevated 1 hour after off CPB and further markedly increased 2 hours after off bypass. Conclusions Fetal CPB could be performed under both hypothermic and normothermic conditions. However, normothermic bypass may provide better delivery of oxygen to fetal tissue.     

Metabolic changes in the lower esophageal sphincter influencing the result of anti-reflux surgical interventions in chronic gastroesophageal reflux disease

AIM: With the availability of a minimally invasive approach, anti-reflux surgery has recently experienced a renaissance as a cost-effective alternative to life-long medical treatment in patients with gastroesophageal reflux disease (GERD). We are not aware of the fact whether reflux episodes causing complaints for a long time i.e., at least for one year are associated with metabolic changes in the lower esophageal sphincter, and if so, whether these may influence functional results achieved after anti-reflux surgery. METHODS: Between 1 January 2001 and 31 December 2002 we performed anti-reflux surgery on 79 patients. Muscle samples were taken from the lower esophageal sphincter (LES) in 33 patients during anti-reflux surgery. Inclusion criteria were: LES resting pressure below 10 mmHg and a marked, pH proven acid exposure to the esophagus of at least one year's duration, causing subjective complaints and requiring continuous proton pump inhibitor treatment. Control samples were obtained from muscle tissue in the gastroesophageal junction that had been removed from 17 patients undergoing gastric or esophageal resection. Metabolic and lysosomal enzyme activities and special protein concentrations 16 parameters in total were evaluated in tissue taken from control specimens and tissue taken from patients with GERD. The biochemical parameters of these intra-operative biopsies were used to correlate the results of anti-reflux operations (Visick Ⅰ and Ⅱ-Ⅲ). RESULTS: In the reflux-type muscle, we found a significant increase of the energy-enzyme activities e.g., creatine kinase, lactate dehydrogenase, β-hydroxybutyrate dehydrogenase, and aspartate aminotransaminase-. The concentration of the structural protein S-100 and the myofibrillar protein troponin Ⅰ were also significantly increased. Among lysosomal enzymes, we found that the activities of cathepsin B, tripeptidyl-peptidase Ⅰ, dipeptidyl-peptidase Ⅱ, β-hexosaminidase B, β-mannosidase and β-galactosidase were significantly decreased as compared to the control LES muscles. By analyzing the activity values of the 9 patients in Visick groups Ⅱ and Ⅲ at two months post-surgery, we found a significant increase in the activity of the so-called energy-enzyme values and in the concentration of structural and myofibrillar proteins as compared to the rest of the reflux patients. CONCLUSION: Our results call attention to the metabolic changes that occurred in the LES muscles of reflux patients. The developing hypertrophy-like changes of LES muscles may be a reason for complaints after anti-reflux surgery, which consisted mainly of reports of persisting dysphagia.     

Visceral response to acute retrograde gastric electrical stimulation in healthy human

AIM: To investigate the visceral response to acute retrograde gastric electrical stimulation (RGES) in healthy humans and to derive optimal parameters for treatment of patients with obesity. METHODS: RGES with a series of effective parameters were performed via a bipolar mucosal electrode implanted along the great curvature 5 cm above pylorus of stomach in 12 healthy human subjects. Symptoms associated with dyspepsia and other discomfort were observed and graded during RGES at different settings, including long pulse and pulse train. Gastric myoelectrical activity at baseline and during different settings of stimulation was recorded by a multi-channel electrogastrography. RESULTS: The gastric slow wave was entrained in all the subjects at the pacing parameter of 9 cpm in frequency, 500 ms in pulse width, and 5 mA in amplitude. The frequently appeared symptoms during stimulation were satiety, bloating, discomfort, pain, sting, and nausea. The total symptom score for each subject significantly increased as the amplitude or pulse width was adjusted to a higher scale in both long pulse and pulse train. There was a wide diversity of visceral responses to RGES among individuals. CONCLUSION: Acute RGES can result in a series of symptoms associated with dyspepsia, which is beneficial to the treatment of obesity. Optimal parameter should be determined according to the individual sensitivity to electrical stimulation.     

生长抑素、胃动素在人胎儿消化系统的发生与分布

目的：了解并比较生长抑素（ＳＳ）、胃动素（ＭＴＬ）在人胚胎消化系统发生、发展及分布的规律。方法：应用放射免疫分析法（ＲＩＡ）系统测定１５例人胎儿消化道各部位ＳＳ及ＭＴＬ的组织含量。结果：在人胚胎胃肠道组织中均有不同浓度的ＳＳ和ＭＴＬ存在，ＳＳ在消化道出现的时间均早于１６周；ＭＴＬ除食管、贲门、幽门、盲肠、阑尾晚于２２周，其余均早于１６周。各部位ＳＳ含量以十二指肠、胃较高，与其它部位比较Ｐ＜０．０５，而ＭＴＬ以空肠、十二指肠为高（Ｐ＜０．０５）。随胚胎发育，ＳＳ的发展呈不同趋势：①胃、十二指肠、空肠ＳＳ持续升高，且胃、十二指肠ＳＳ浓度与胎龄呈正相关（ｒ＝０．８０７７；ｒ＝６７９３；Ｐ＜０．０１）；②食管、回肠、结肠ＳＳ波动在一定水平，变化无显著性差异（Ｐ＞０．０５）；③贲门、幽门、盲肠、阑尾ＳＳ则呈下降趋势，阑尾ＳＳ与胎龄呈负相关（ｒ＝－０．７８８９；Ｐ＜０．０１）；而ＭＴＬ各部位水平随胚胎发育呈一致性升高，空肠、十二指肠ＭＴＬ与胎龄呈正相关（ｒ＝０．８１２５，ｒ＝０．７７３４，Ｐ＜０．０１）。结论：ＳＳ与ＭＴＬ在人胎儿胃肠道中的发生、发展及分布存在不同规律     

Ghrelin gene expression is markedly higher in fetal pancreas compared with fetal stomach: effect of maternal fasting

Ghrelin is an orexigenic peptide secreted mainly by the stomach in adult rats. Ghrelin concentrations increase with fasting and decrease after food intake. Ghrelin is also present in the placenta and in the fetal stomach, but the role of fetal ghrelin remains unclear. In this study, we compared changes in plasma ghrelin, insulin, and glucose concentrations and in ghrelin gene expression in stomach, pancreas, and placenta in response to fasting and feeding in adult nonpregnant rats and in 20-d pregnant dams and their fetuses. Plasma total ghrelin concentrations were three times higher in the fetus than in the dam but did not increase in response to fasting. In contrast to total ghrelin, plasma active ghrelin concentrations wee 50% lower in the fetus compared with the adult pregnant rat. Ghrelin mRNA and total ghrelin were markedly elevated in the fetal pancreas and six to seven times greater than in the fetal stomach but were not affected by fasting. In contrast, fetal pancreas and stomach active ghrelin concentrations increased two to three times after maternal fasting. Ghrelin receptor mRNA was present in all fetal pancreas samples. Placenta ghrelin gene expression was detectable but low. These data raise the possibility that in the fetus, in contrast to the adult, the pancreas and not the stomach is a major source of circulating immunoreactive ghrelin. Furthermore, the presence of a strong ghrelin gene expression and of ghrelin receptor mRNA in the fetal pancreas is intriguing and suggests that ghrelin may play an important role in beta-cell development.     

Appearance of gastrin and somatostatin in the human fetal stomach, duodenum and pancreas.

The gestational time of appearance of gastrin and somatostatin in the human fetal stomach, duodenum and pancreas was examined. Immunoreactive gastrin (IRG) is detected in antral, duodenal and pancreatic extracts of a 7.0-cm (crown-heel length) fetus. More IRG is extracted from the duodenum than the antrum. Duodenal IRG concentration from fetuses of 16.0--26.0 cm are higher than younger fetal and adult concentrations. Antral IRG concentrations are one tenth of the adult contents. Very small IRG concentrations are present in the human fetal pancreas. Gastrin immunohistochemical staining is positive first in duodenal (6.5-cm fetus) and later in antral (12.5-cm fetus) mucosa; pancreatic tissue is negative for gastrin immunohistochemistry. Type IV cells are encountered in antral and duodenal mucosa of 4.0-cm fetuses; other endocrine cells appear with fetal growth. Not until much later in gestation (21.0 cm) do typical G cells appear. These results suggest that early in fetal life gastrin is produced by the type IV cell. Somatostatin immunohistochemical staining is positive in stomach, duodenum and pancreas in 6.5-cm fetuses. Immature D cells are found in antral and duodenal mucosa of 5.0-cm fetuses and mature D cells in 11.0-cm fetuses.     

Noninvasive prenatal diagnosis of hemophilia by microfluidics digital PCR analysis of maternal plasma DNA

Hemophilia is a bleeding disorder with X-linked inheritance. Current prenatal diagnostic methods for hemophilia are invasive and pose a risk to the fetus. Cell-free fetal DNA analysis in maternal plasma provides a noninvasive mean of assessing fetal sex in such pregnancies. However, the disease status of male fetuses remains unknown if mutation-specific confirmatory analysis is not performed. Here we have developed a noninvasive test to diagnose whether the fetus has inherited a causative mutation for hemophilia from its mother. The strategy is based on a relative mutation dosage approach, which we have previously established for determining the mutational status of fetuses for autosomal disease mutations. In this study, the relative mutation dosage method is used to deduce whether a fetus has inherited a hemophilia mutation on chromosome X by detecting whether the concentration of the mutant or wild-type allele is overrepresented in the plasma of heterozygous women carrying male fetuses. We correctly detected fetal genotypes for hemophilia mutations in all of the 12 studied maternal plasma samples obtained from at-risk pregnancies from as early as the 11th week of gestation. This development would make the decision to undertake prenatal testing less traumatic and safer for at-risk families.     

Prenatal diagnosis of thyroid hormone resistance

A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor beta (TRbeta) gene. She presented with symptoms and signs of hyperthyroidism and was successfully treated with 3,5,3'-triiodothyroacetic acid (TRIAC) until the onset of pregnancy. This therapy was then discontinued in order to prevent TRIAC, a compound that crosses the placental barrier, from exerting adverse effects on normal fetal development. However, as the patient showed a recurrence of thyrotoxic features after TRIAC withdrawal, we sought to verify, by means of genetic analysis and hormone measurements, whether the fetus was also affected by RTH, in order to rapidly reinstitute TRIAC therapy, which could potentially be beneficial to both the mother and fetus. At 17 weeks gestation, fetal DNA was extracted from chorionic villi and was used as a template for PCR and restriction analysis together with direct sequencing of the TRbeta gene. The results indicated that the fetus was also heterozygous for the T337A mutation. Accordingly, TRIAC treatment at a dose of 2.1 mg/day was restarted at 20 weeks gestation. The mother rapidly became euthyroid, and the fetus grew normally up to 24 weeks gestation. At 29 weeks gestation mild growth retardation and fetal goiter were observed, prompting cordocentesis. Circulating fetal TSH was very high (287 mU/L) with a markedly reduced TSH bioactivity (B/I: 1.1 +/- 0.4 vs 12.7 +/- 1.2), while fetal FT4 concentrations were normal (8.7 pmol/L; normal values in age-matched fetuses: 5-22 pmol/L). Fetal FT3 levels were raised (7.1 pmol/L; normal values in age-matched fetuses: <4 pmol/L), as a consequence of 100% cross-reactivity of TRIAC in the FT3 assay method. To reduce the extremely high circulating TSH levels and fetal goiter, the dose of TRIAC was increased to 3.5 mg/day. To monitor the possible intrauterine hypothyroidism, another cordocentesis was performed at 33 weeks gestation, showing that TSH levels were reduced by 50% (from 287 to 144 mU/L). Furthermore, a simultaneous ultrasound examination revealed a clear reduction in fetal goiter. After this latter cordocentesis, acute complications occured, prompting delivery by cesarean section. The female neonate was critically ill, with multiple-organ failure and respiratory distress syndrome. In addition, a small goiter and biochemical features ofhypothyroidism were noted transiently and probably related to the prematurity of the infant. At present, the baby is clinically euthyroid, without goiter, and only exhibits biochemical features of RTH. In summary, although further fetal studies in cases of RTH are necessary to determine whether elevated TSH levels with a markedly reduced bioactivity are a common finding, our data suggest transient biochemical hypothyroidism in RTH during fetal development. Furthermore, we advocate prenatal diagnosis of RTH and adequate treatment of the disease in case of maternal hyperthyroidism, to avoid fetal thyrotrope hyperplasia, reduce fetal goiter, and maintain maternal euthyroidism during pregnancy.     

Hematopoietic progenitor cells as targets for non-invasive prenatal diagnosis: detection of fetal CD34+ cells and assessment of post-delivery persistence in the maternal circulation

Culture expansion of fetal cells from the maternal circulation will provide an increased number of cells for non-invasive prenatal diagnosis. Hematopoietic CD34+ cells are potential candidates for this application. More information is needed regarding the frequency of these cells and the phenomenon of post-delivery persistence in the maternal circulation. In this study we assessed the number of fetal CD34+ cells in the maternal circulation, the effect of culture expansion on the number of fetal cells and the persistence of fetal CD34+ cells from previous pregnancies. Fetal cells were identified by the presence of Y-chromosome sequences detected by FISH and nested PCR. Fetal CD34+ cells were detected in all samples from women carrying a male fetus. A low number of residual fetal cells from previous pregnancies was detected (1-3 XY cells in 20 ml blood) in less than 1/3 of the samples from both non-pregnant women and those pregnant with a female fetus. Culturing of CD34+ cells resulted in a significant increase in fetal cell numbers. However, the number of fetal cells persisting from previous pregnancies also increased after culture. It is proposed that information derived from CD34+ cells could potentially support data derived from other cell types for more accurate non-invasive prenatal diagnosis.     

Fetal ventricular pacing for hydrops secondary to complete atrioventricular block

The advent of ultrasound recording has expanded the capabilities for treatment of the fetus in utero. The diagnosis of specific disease processes has allowed for prenatal intervention by new techniques designed to improve fetal survival. The application of ventricular pacing in a hydropic fetus with complete atrioventricular (AV) block is reported. Complete AV block resulted from maternal collagen vascular disease. The application of ventricular pacing was to allow for further in utero development and for reversal of hydrops fetalis after improvement in cardiac output. Despite fetal death 4 hours after placement of the ventricular pacing lead, this procedure when applied earlier in the development of hydrops may allow for fetal survival. Ventricular pacing was accomplished without apparent trauma to mother or fetus and no evidence of fetal injury was seen at necropsy. Therefore, in the fetus who would otherwise die in utero before the point of viability ex utero, fetal ventricular pacing may be a rational alternative to current observation.     

Developmental onset of cardiovascular disease—Could the proof be in the placenta?

The Barker Hypothesis states change to the maternal environment may have significant impacts on fetal development, setting the stage for adult disease to occur. The development of the maternofetal vasculature during implantation and maintenance during pregnancy is extremely precise, yet dynamic. Delays or dysfunction in the orchestration of anatomical remodeling, maintenance of blood pressure, or responsiveness to metabolic demand may have severe consequences to the developing fetus. While these intermissions may not be fatal to the developing fetus, an interruption, reduction, or an inability to meet fetal demand of blood flow during crucial stages of development may predispose young to disease later in life. Maternal inability to meet fetal demand can be attributed to improper placental development and vascular support through morphological change or physiological function will significantly limit nutrient delivery and waste exchange to the developing fetus. Therefore, we present an overview of the uteroplacental vascular network, maternal cardiovascular adaptations that occur during pregnancy, placental blood flow, and common maternal comorbidities and/or exposures that may perturb maternal homeostasis and affect fetal development. Overall, we examine uterine microvasculature pathophysiology contributing to a hostile gestational environment and fetal predisposition to disease as it relates to the Barker Hypothesis.     

孕妇血浆游离胎儿DNA检测在唐氏综合征筛查中的应用价值

目的通过检测唐氏综合征（DS）孕妇血浆中的游离胎儿DNA（iDNA）含量,寻找一种产前筛查DS的新方法。方法选择DS男胎孕妇5例、Ds高危男胎孕妇21例、正常男胎孕妇22例,用QIAampDNABloodKit提取孕妇血浆中tDNA,并用TagMan探针实时定量RT-PCR技术进行检测,以Y染色体上的DYS14基因作为男性fDNA的标记物。结果DS孕妇血浆中fDNA为（127．4±58．4）GF／ml,DS高危孕妇为（78．4±28．0）GE／ml,正常孕妇为（48．5±20．8）GE／ml,两两比较,P均〈0．01。结论孕妇血浆中游离tDNA定量检测可以作为产前筛查DS的候选指标。     

Carrier detection and prenatal diagnosis of hemophilia B with more advanced techniques

Summary We used the PCR to amplify three polymorphic regions of Factor IX gene on 35 Italian families: DdeI intron 1, MnlI exon f, and the polymorphism HhaI located 8 kb at the 3 end of FIX gene. We analyzed the MnlI and HhaI markers on DGGE and DdeI polymorphism on agarose gel. We reached an informativity of 78% and we found one mutation at codon 145 (exon f) during the screening for MnlI polymorphism. Furthermore, we performed 16 prenatal diagnoses on chorionic villus samples; five were female and 11 male. Four were uninformative three healthy and one affected male fetus were recognized by PCR techniques, two healthy and one affected fetus by Southern analysis. In three pregnant women examined for the first time during pregnancy, the PCR technique allowed us to perform a rapid diagnosis of noncarrier status, avoiding the fetal sampling procedures.