Spontaneously ruptured gastrointestinal stromal tumor (GIST) of the jejunum mimicking acute appendicitis

Gastrointestinal stromal tumors (GISTs) are characterized with diverse clinical presentations, including acute and chronic gastrointestinal bleeding, abdominal pain, presence of an intra-abdominal mass, anorexia, and intestinal obstruction. A 60-year-old obese woman presented as an acute abdominal emergency with right lower quadrant (RLQ) pain and tenderness, nausea and leukocytosis, all mimicking acute appendicitis. Laparotomy revealed a spontaneously ruptured GIST of the jejunum, which was localized to the RLQ due to postoperative adhesions following previous two cesarean sections and cholecystectomy. Complete surgical resection was performed, followed by an uneventful early postoperative course.     

腹腔镜与开放手术治疗复杂性阑尾炎的疗效比较

目的:观察和比较腹腔镜与开放手术治疗复杂性阑尾炎的临床效果及安全性。方法:选取2012年4月~2014年5月于我院(总院及分院)诊治的复杂性阑尾炎患者共131例,按照随机原则分为对照组65例和观察组66例,对照组实施开腹阑尾切除术治疗,观察组实施腹腔镜阑尾切除术治疗。对比两组患者各项术中、术后临床指标。结果:两组的手术时间比较无明显差异(P0.05);观察组患者的手术切口长度、术中出血量、术后肠功能恢复时间、置管引流时间、术后24 h VAS、住院时间均明显优于对照组,差异具有统计学意义(P0.05);观察组(12.1%)并发症总发生率低于对照组(27.7%)(P0.05)。两组肠梗阻发生率相近,无明显差异(P0.05)。结论:腹腔镜手术治疗复杂性阑尾炎较开腹阑尾切除术具有创伤小、出血少、疼痛轻、住院时间短、恢复快的优势,且安全性更高。     

Mechanisms of neonatal mucosal antibody protection

Following an abrupt transition at birth from the sterile uterus to an environment with abundant commensal and pathogenic microbes, neonatal mammals are protected by maternal Abs at mucosal surfaces. We show in mice that different Ab isotypes work in distinct ways to protect the neonatal mucosal surface. Secretory IgA acts to limit penetration of commensal intestinal bacteria through the neonatal intestinal epithelium: an apparently primitive process that does not require diversification of the primary natural Ab repertoire. In contrast, neonatal protection against the exclusively luminal parasite Heligmosomoides polygyrus required IgG from primed females. This immune IgG could either be delivered directly in milk or retrotransported via neonatal Fc receptor from the neonatal serum into the intestinal lumen to exert its protective effect.     

Stereological analysis of peroxisomes and mitochondria in intestinal epithelium of patients with peroxisomal deficiency disorders: Zellweger's syndrome and neonatal-onset adrenoleukodystrophy

Peroxisomes, participants in lipid metabolism, have been shown to be altered in liver in two metabolic diseases in which long-chain fatty acids accumulate in tissues: Zellweger's syndrome and neonatal adrenoleukodystrophy (ALD). The intestine also plays a role in lipid metabolism, and we have had the opportunity to compare peroxisomes in normal intestinal epithelium with those from patients with Zellweger's syndrome and neonatal ALD at the electron microscopic level by using the combined techniques of cytochemistry and stereological analysis. Peroxisomes were numerous in intestinal epithelium of the normal individuals. They were ellipsoidal in shape with average diameters of 0.37 by 0.56 micron and filled with coarsely granular, DAB+ content. Peroxisomes in the intestinal epithelium of the ALD patient were similar in appearance and number but smaller in size (0.28 by 0.44 micron). Peroxisomes of normal appearance were absent from the intestinal epithelium of patients with Zellweger's syndrome; DAB+ content, however, was observed in rare, membrane-bound structures of much smaller size (0.12 by 0.19 micron). In liver of patients with Zellweger's syndrome, peroxisomes are lacking; in neonatal ALD they are abnormal in appearance and greatly reduced in number. The presence of rare minute peroxisomes in the intestinal epithelium in Zellweger's syndrome and of small peroxisomes in this epithelium in neonatal ALD indicate that peroxisomes in the intestinal epithelium are affected in these diseases, but to a lesser extent than in the liver. In the ALD intestinal epithelium, DAB+ material was also seen in long, sinuous, tubular or cisternal elements intermingled and occasionally in continuity with peroxisomes. It is suggested that these represent the early stages of peroxisome formation, the peroxisomal reticulum as originally envisioned by Lazarow, while the rare structures seen in Zellweger's represent rudiments of such a reticulum. Lamellar inclusions and clear spaces occurred in the cytoplasm adjacent to these structures indicating either that material accumulated there had been extracted during fixation or that these regions are more susceptible to autolysis. Mitochondria are also involved in lipid metabolism and have been reported to be abnormal in Zellweger's tissue. No qualitative differences were observed in the mitochondria of the intestinal epithelia examined in this study. Although quantitation revealed a greater mean volume, number, and surface density of mitochondria in the intestinal epithelia of neonatal ALD, it was not a statistically significant difference in all cases.     

腹腔镜阑尾切除术与开腹阑尾切除术治疗急性阑尾炎的疗效比较

目的:比较腹腔镜阑尾切除术和开腹阑尾切除术治疗急性阑尾炎的临床疗效。方法:选取2012年3月-2014年3月我院收治的急性阑尾炎患者127例,按照随机数字表法分为两组,观察组63例行腹腔镜阑尾切除手术,对照组64例行开腹阑尾切除手术,比较两组的手术效果及术后并发症情况。结果:两组的手术时间差异无统计学意义(P0.05),观察组术中出血量、肛门排气时间及住院时间均低于对照组,差异有统计学意义(P0.05)。两组治疗后VAS评分较治疗前有不同程度的降低,且观察组低于对照组,差异有统计学意义(P0.05)。观察组切口感染、肠梗阻以及腹腔脓肿发生率均低于对照组,差异有统计学意义(P0.05),而两组腹腔内出血、阑尾残端瘘的发生率比较,差异无统计学意义(P0.05)。结论:腹腔镜阑尾切除术治疗急性阑尾炎具有手术效果好、预后快及术后并发症少等特点,值得临床推广使用。     

Polyinosinic-polycytidylic acid accelerates intestinal stem cell proliferation via modulating Myc expression

It is well known that exposure of double-stranded RNA (dsRNA) to intestine immediately induces villus damage with severe diarrhea, which is mediated by toll-like receptor 3 signaling activation. However, the role of intestinal stem cells (ISCs) remains obscure during the pathology. In the present study, polyinosinic-polycytidylic acid (poly[I:C]), mimicking viral dsRNA, was used to establish intestinal damage model. Mice were acutely and chronically exposed to poly(I:C), and ISCs in jejunum were analyzed. The results showed that the height of villus was shorter 48 hr after acute poly(I:C) exposure compared with that of controls, while chronic poly(I:C) treatment increased both villus height and crypt depth in jejunum compared with control animals. The numbers of ISCs in jejunum were significantly increased after acute and chronic poly(I:C) exposure. Poly (I:C)-stimulated ISCs have stronger capacities to differentiate into intestine endocrine cells. Mechanistically, poly(I:C) treatment increased expression of Stat1 and Axin2 in the intestinal crypt, which was along with increased expression of Myc, Bcl2, and ISC proliferation. These findings suggest that dsRNA exposure could induce ISC proliferation to ameliorate dsRNA-induced intestinal injury.     

Maternal deprivation affects the neuromuscular protein profile of the rat colon in response to an acute stressor later in life

Early life stress as neonatal maternal deprivation (MD) predisposes rats to alter gut functions in response to acute psychological stressors in adulthood, mimicking features of irritable bowel syndrome (IBS). We applied proteomics to investigate whether MD permanently changes the protein profile of the external colonic neuromuscular layer that may condition the molecular response to an acute stressor later in life.

Male rat pups were separated 3 h/day from their mothers during the perinatal period and further submitted to water avoidance (WA) stress during adulthood. Proteins were extracted from the myenteric plexus-longitudinal muscle of control (C), WA and MD + WA rat colon, separated on 2D gels, and identified by mass spectrometry. MD amplified the WA-induced protein changes involved in muscle contractile function, suggesting that stress accumulation along life imbalances the muscle tone towards hypercontractility. Our results also propose a stress dependent regulation of gluconeogenesis. Secretogranin II – the secretoneurin precursor – was induced by MD. The presence of secretoneurin in myenteric ganglia may partially explain the stress-mediated modulation of gastrointestinal motility and/or mucosal inflammation previously described in MD rats.

In conclusion, our findings suggest that neonatal stress alters the responses to acute stress in adulthood in intestinal smooth muscle and enteric neurons.     

血清降钙素原检测在老年人急性阑尾炎中的临床价值

目的:探讨降钙素原(PCT)的检测在老年人急性阑尾炎诊断中的价值。方法:检测96例在我院进行阑尾切除术的急性阑尾炎和误诊为急性阑尾炎的老年患者以及20例健康体检者血清PCT水平。结果:急性坏疽性阑尾炎及急性化脓性阑尾炎患者术前血清PCT值均较健康对照、阑尾无炎症及急性单纯性阑尾炎患者明显升高(P<0.01);而急性单纯性阑尾炎、阑尾无炎症患者与健康对照三者之间无明显差异(P>0.05);阑尾切除术后血清PCT值呈逐渐下降趋势(P<0.01)。结论:在临床症状及白细胞计数升高、BUS帮助的基础上,结合血清PCT的测定对老年人急性阑尾炎的诊断具有一定价值。     

Excitotoxin-Induced Neuronal Death Is Associated with Response of a Unique Intracellular Aspartic Proteinase, Cathepsin E

Abstract: Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white matter lesions mimicking periventricular leukomalacia, the most frequent brain lesion occurring in premature human babies. In this model, coinjection of vasoactive intestinal peptide prevents white matter lesions. In the present study, coadministration of ibotenate, vasoactive intestinal peptide, and selective transduction inhibitors showed that protein kinase C and mitogen-associated protein kinase pathways were critical for neuroprotection. In vivo and in vitro immunocytochemistry revealed that vasoactive intestinal peptide activated protein kinase C in astrocytes and neurons, and mitogen-associated protein kinase in neurons. In vitro neuronal transduction activation was indirect and required medium conditioned by astrocytes in which protein kinase C had been activated by vasoactive intestinal peptide. Although vasoactive intestinal peptide did not prevent the initial in vivo appearance of white matter lesion, it promoted a secondary repair of this lesion with axonal regrowth. Through protein kinase C activation, vasoactive intestinal peptide also prevented ibotenate-induced white matter astrocyte death. These data support the following hypothetical model: Vasoactive intestinal peptide activates protein kinase C in astrocytes, which promotes astrocytic survival and release of soluble factors; these released factors activate neuronal mitogen-associated protein kinase and protein kinase C, which will permit axonal regrowth.     

Clinical analysis of the related factors in acute appendicitis

BACKGROUND: In order to determine reliable clues for early diagnosis of acute appendicitis, this study was conducted to examine the related factors in patients with clinically suspected acute appendicitis. METHODS: We retrospectively analyzed 282 patients with the clinical diagnosis of acute appendicitis at China Medical College Hospital in Taiwan from January to December 2000. To study the significant related factors of acute appendicitis, the t-test, chi-square analysis, and multivariate logistic regression analysis were used. RESULTS: There were 153 males (54.3 percent) and 129 females (45.7 percent). The mean age was 30.3+/-17.4 years (range 1 to 81). The diagnostic rate of acute appendicitis was 86.2 percent. If the combination of elevated C-reactive protein, leukocytosis and elevated neutrophil ratio was used, satisfactory specificity and positive predictive value were achieved in diagnosing acute appendicitis. After controlling for the other covariates, the multivariate logistic regression analysis showed that the significant related factors of acute appendicitis were male sex (odds ratio = 3.4; 95 percent confidence interval = 1.6 to 7.3; p <0.01) and elevated neutrophil ratio (odds ratio = 4.6; 95 percent confidence interval = 2.0 to 10.6; p <0.001). CONCLUSIONS: If an elevated neutrophil ratio was observed, the probability of acute appendicitis was increased in patients with clinically suspected acute appendicitis. Thus, neutrophil ratio appears to be a good parameter for diagnosis of acute appendicitis in primary healthcare settings.     

Autophosphorylation of Polo-like Kinase 4 and Its Role in Centriole Duplication

Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase activity is essential for centriole duplication. Here, we show that PLK4 autophosphorylation of serine S305 is a consequence of kinase activation and enables the active fraction to be identified in the cell. Active PLK4 is detectable on the replicating mother centriole in G1/S, with the proportion of active kinase increasing through interphase to reach a maximum in mitosis. Activation of PLK4 at the replicating daughter centriole is delayed until G2, but a level equivalent to the replicating mother centriole is achieved in M phase. Active PLK4 is regulated by the proteasome, because either proteasome inhibition or mutation of the degron motif of PLK4 results in the accumulation of S305-phosphorylated PLK4. Autophosphorylation probably plays a role in the process of centriole duplication, because mimicking S305 phosphorylation enhances the ability of overexpressed PLK4 to induce centriole amplification. Importantly, we show that S305-phosphorylated PLK4 is specifically sequestered at the centrosome contrary to the nonphosphorylated form. These data suggest that PLK4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication.     

Differential transmission of HIV traversing fetal oral/intestinal epithelia and adult oral epithelia

While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4(+) T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT.     

Imprinting of a small nucleolar RNA gene on mouse chromosome 12

We have identified a novel, maternally expressed imprinted gene encoding a C/D-box small nucleolar RNA (snoRNA) called MBII-343, which may regulate RNA editing or alternative splicing of an as yet unknown target gene. This gene is closely linked to an imprinted gene, Meg3, on mouse distal chromosome 12, which is syntenic to human chromosome 14. The paternal duplication of mouse distal chromosome 12 leads to late embryonal/neonatal lethality, growth promotion, and cardiomyopathy, whereas maternal duplication leads to late embryonal lethality and growth retardation. Human paternal uniparental disomy for chromosome 14 leads to musculoskeletal problems and mental retardation, whereas maternal uniparental disomy leads to intrauterine growth retardation, motor developmental delay, premature puberty, hypotonia, joint laxity, macrocephaly, short statue, neonatal poor sucking, skill with jigsaw puzzles, skin picking, obesity, and maturity onset diabetes of the young.     

Complex control of mouse apolipoprotein B gene expression revealed by targeted duplication

An elevated plasma level of apolipoprotein B-containing lipoproteins is a risk factor for atherosclerotic cardiovascular disease. Subtle genetic abnormalities in gene expression including an increased expression of the APOB gene may play an important role in determining overall risk. In an attempt to increase mouse Apob expression, we used gene targeting and duplicated approximately 65 kb of genomic DNA containing the Apob locus in its natural genomic position in mice. While we successfully generated mice carrying the Apob gene duplication, the amount of the total Apob mRNA was not increased in their liver. In the intestine, total Apob mRNA was reduced to half of the wild-type mice. Plasma lipids in the Apob duplication mice were not altered. Expression analyses showed that the proximal Apob gene in the duplicated locus was preferentially expressed in both tissues suggesting a limitation of tissue-specific enhancer function. The previously characterized distant intestinal control element was not duplicated, explaining the unequal ratio of intestinal Apob expression. While the existence of an additional liver-specific enhancer element is unknown, our findings suggest the presence of an additional enhancer outside the duplicated region, and that Apob gene expression is more complicated than previously thought.     

Schistosomal appendicitis: Case series and systematic literature review

BackgroundGlobally, schistosomiasis affects at least 240 million people each year with a high proportion of cases in sub-Saharan Africa. The infection presents a wide range of symptoms mainly at the gastrointestinal and urogenital level. Cases of schistosomiasis-related appendicitis are seldom reported. The aim of the present study is to identify the prevalence of schistosomiasis-related appendicitis in Beira, Mozambique and compare to global prevalence.MethodsWe retrospectively reviewed all cases of appendicitis recorded from January 2017 to March 2020 at a single pathology department located in Beira in order to assess the prevalence of schistosomiasis. Moreover, we performed a systematic review on the prevalence of schistosomiasis-related appendicitis in all countries.FindingsA total of 145 appendicitis cases in Beira showed a 13.1% prevalence of schistosomal-related appendicitis. The mean age of patients was 29.1 years, and 14 (73.7%) were male. The systematic review identified 20 studies with 34,790 inpatients with schistosomiasis-related appendicitis with a global prevalence of 1.31% (95% confidence interval (CI): 0.72 to 2.06); a high heterogeneity (I² = 96.0%) was observed. Studies carried out in Africa reported a significantly higher prevalence of schistosomiasis-related appendicitis (2.75%; 95% CI: 1.28 to 4.68) than those in Middle East (0.49%; 95% CI: 0.18 to 0.95) (p for interaction < 0.0001).ConclusionsSchistosomiasis infection should be considered as possible cause of appendicitis not only in endemic areas but also in developed countries. Considering that prevention is the best way to control the infection, more efforts should be put in place in order to increase the prevention coverage and avoid the cascading implications for health. This is even more so important in this Coronavirus Disease 2019 (COVID-19) era where the majority of attention and funds are used to fight the pandemic.     

Characteristic transport of lactoferrin from the intestinal lumen into the bile via the blood in piglets

Lactoferrin is a major iron-binding protein in milk from several species, such as humans, monkeys, mice and sows. Using neonatal and weaner piglets, the characteristic transfer of lactoferrin from intestinal lumen into bile via the circulation was investigated. Bovine lactoferrin (1 or 3 g/kg body weight) was infused into the stomach through a polyethylene tube or into the duodenum through a duodenal catheter over 5 min. Peripheral blood and bile samples were collected after the infusion. Lactoferrin absorbed into plasma and bile were assayed quantitatively by double-antibody enzyme-linked immunosorbent assay, and homogeneity of bovine lactoferrin in plasma and bile was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting methods. Morphological investigation was carried out according to the peroxidase anti-peroxidase method. Following oral administration in neonatal pigs, bovine lactoferrin appeared in the blood circulation and reached a peak level after 2 h. It was confirmed immunohistochemically that lactoferrin was transported by endocytosis via the epithelial cells. Lactoferrin absorbed into the blood was also detected in the bile and reached a peak value 12 h after oral administration. Transportation of lactoferrin from the intestinal lumen into the bile via the bloodstream was also observed in weaner piglets. Lactoferrin transported into plasma and bile was confirmed to be the same substance as administrated lactoferrin by electrophoresis and immunoblotting methods. Lactoferrin transported into bile was re-absorbed into the blood in neonatal pigs. These results demonstrate that lactoferrin contained in milk is transported into the circulation from the intestinal lumen and excreted into the bile, suggesting the possibility of entero-hepatic circulation of lactoferrin in neonatal pigs.     

Effect of age on vasoactive intestinal polypeptide-induced short-circuit current in porcine jejunum

Vasoactive intestinal polypeptide is a transmitter at the neuroepithelial junction of the small intestine in cholera toxin-induced secretion. We investigated whether the secretory effect in vitro of vasoactive intestinal polypeptide in porcine jejunum was changed with age. Stripped tissue preparations from three age groups, neonatal (7-11 days), young (6-8 weeks) and adult (13-15 weeks) pigs, were mounted in Ussing chambers and short-circuited. Vasoactive intestinal polypeptide produced concentration dependent increases in short-circuit current in all three age groups with EC50 values (in nM) of 14.5 +/- 1.9, 16.2 +/- 2.0 and 147 +/- 0 in neonatal, young and adult pigs, respectively. The peak increases in short-circuit current in adult pigs were significantly decreased compared with the other two age groups. To evaluate the secretory capacity, theophylline was added to tissue preparations in which baseline short-circuit current again was established. Theophylline caused a significantly lesser increase in short-circuit current in adult pigs (25.4 +/- 2.0 microA.cm-2) than neonatal (57.1 +/- 3.6 microA.cm-2) and young pigs (63.1 +/- 2.9 microA.cm-2). In conclusion, vasoactive intestinal polypeptide showed a marked decrease in the secretory response with age in porcine jejunum, at least partly caused by a reduced secretory capacity of the enterocytes.     

Small intestinal and pancreatic microstructures are modified by an intraduodenal CCK-A receptor antagonist administration in neonatal calves

The aim of the present study was to investigate the role of CCK on the upper gut and pancreas microstructure and on pancreatic juice secretion in neonatal calves assessed by a repetitive intraduodenal administration of FK480, a CCK-A receptor antagonist, during the first 6 days of life. The experiment was performed on 10 neonatal calves surgically fitted with a pancreatic accessory duct catheter and duodenal cannulas. Calves were sacrificed on day 7 for tissue sampling. Treatment with FK480 resulted in: reduction of preprandial pancreatic juice secretion at days 1-3, smaller size of pancreatic acini and number of cells per acinus, reduction in intestinal crypt depth (except in the duodenal bulb), numerous modifications of intestinal villi length and width, lower mitotic index of crypt cells, and increased number and size of enterocytes with 'empty vacuoles'. In conclusion, the blockade of CCK-A receptors during early life both reduced pancreatic exocrine secretion and induced complex changes in pancreatic microstructure. The influence of CCK on the upper gut microstructure in neonatal calves could be either direct via activation of CCK-A receptors located in the mucosa of the upper gut or indirect by modulation of the secretion of pancreatic juice.