Postnatal treatment and evolution patterns of giant fetal hepatic hemangioma: a case series of 29 patients.

OBJECTIVES: To explore the clinical characteristics, postnatal treatment and prognosis of giant fetal hepatic hemangioma (GFHH). METHOD: Retrospective analysis was performed on children with giant fetal hepatic hemangioma (maximum tumor diameter > 40 mm) diagnosed by prenatal ultrasound and MRI from December 2016 to December 2020. These patients were observed and treated at the Children's Hospital of Fudan University after birth. The clinical data were collected to analyze the clinical characteristics, treatment, and prognosis of GFHH using independent sample t tests or Fisher's exact tests. RESULTS: Twenty-nine patients who were detected by routine ultrasound in the second and third trimester of pregnancy with giant fetal hepatic hemangiomas were included. The first prenatal ultrasound diagnosis of gestational age was 34.0 ± 4.3 weeks, ranging from 22 to 39 weeks. Of the patients, 28 had focal GFHHs and 1 had multifocal GFHHs. Surgery was performed, and the diagnosis was confirmed histopathologically in two patients. There were 8 cases with echocardiography-based evidence of pulmonary hypertension, 11 cases had a cardiothoracic ratio > 0.6, and 4 cases had hepatic arteriovenous fistula (AVF). The median follow-up time was 37 months (range: 14-70 months). During the follow-up, 12 patients received medical treatment with propranolol as the first-line therapy. The treatment group had a higher ratio of cardiothoracic ratio > 0.6 (P = 0.022) and lower albumin levels (P = 0.018). Four (14.8%) lesions showed postnatal growth before involuting. Complete response was observed in 13 (13/29) patients, and partial response was observed in 16 (16/29) patients. CONCLUSIONS: Fetal giant hepatic hemangioma is mainly localized, and its clinical outcome conforms to RICH (rapidly involuting) and PICH (partially involuting), but some fetal giant hepatic hemangiomas will continue to grow after birth and then gradually decrease. For uncomplicated giant fetal hepatic hemangioma, postnatal follow-up is the main concern, while those with complications require aggressive medical treatment. Propranolol may have no effect on the volume change of GFHH.

Flagellin maintains eosinophils in the intestine.

Eosinophils (Eos) are the major effector cells in allergic response. The regulation of Eo is not fully understood yet. Flagellin (FGN) has immune regulatory functions. This study aims to elucidate the role of FGN in maintaining Eo at the static status in the intestinal tissues. A mouse food allergy (FA) model was developed. Eo mediator levels in the serum or culture supernatant or intestinal lavage fluids were assessed and used as an indicator of Eo activation. The results showed that less FGN amounts were detected in the FA mouse intestinal tissues, that were negatively correlated with the Eo activation. Mast cell-derived chymase bound FGN to induce FGN degradation. FGN formed complexes with FcγRI on Eos to prevent specific antigens from binding FcγRI, and thus, to prevent Eo activation. Administration of FGN efficiently alleviated experimental FA. In conclusion, FGN plays a critical role in maintaining Eos at static status in the intestine. Administration of FGN can alleviate experimental FA. FGN may be a novel drug candidate to be used in the treatment of Eo-related diseases.

Thoracoabdominal duplication with hematochezia as an onset symptom in a baby: A case report.

BACKGROUND: Alimentary tract duplication is a rare congenital disease that may occur in any part of the alimentary tract, whereas thoracoabdominal duplications only account for approximately 2% of all alimentary tract duplication cases. Many symptoms, including abdominal pain, abdominal distension, vomiting, gastrointestinal bleeding, chest discomfort, chest pain, and shortness of breath, may be present in patients with abdominal or thoracic duplication. CASE SUMMARY: A 10-mo-old infant, with a free previous medical history, was admitted to our hospital with melena three times in 6 d. Enhanced magnetic resonance imaging of the thoracic vertebrae revealed multiple cervicothoracic vertebral deformities, spina bifida, meningomyelocele towards the posterior mediastinum, and possible concurrent infection. Upper gastroenterography indicated intestinal malrotation. A laparoscopic abdominal examination was performed, and the operation was intraoperatively converted to laparotomy. This case was diagnosed intraoperatively as thoracoabdominal intestinal duplication. The intestinal duplications in the abdomen and large part of the thorax were excised. The results of postoperative pathological examination confirmed that this case was alimentary tract duplication and that part of the duplication contained gastric mucosa. The infant recovered well and was discharged 1 wk after the surgery. A follow-up computed tomography scan 3 mo after operation showed myelomeningocele while the posterior mediastinal cyst was significantly reduced. CONCLUSION: Thoracoabdominal duplication should be considered if a child has suspected abdominal intestinal duplication with hematochezia as an onset symptom.

Vasoactive intestinal peptide alleviates food allergy via restoring regulatory B cell functions.

The immune regulatory cell dysfunction is associated with many immune diseases including food allergy (FA). This study aims to investigate the role of vasoactive intestinal peptide (VIP) in the maintenance of regulatory B cell (Br cell)'s immune suppressive functions by stabilizing thrombospondin (TSP1) expression. In this study, blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. Br cells were isolated from the samples through flow cytometry cell sorting and analyzed by immunological approaches to determine the immune regulatory capacity. We found that the immune suppressive functions of Br cells were impaired in FA patients. The serum VIP levels were associated with the production of immune suppressive function-related mediators (interleukin-10, IL-10) of Br cells in FA patients. VIP counteracted IL-10 mRNA decay in Br cells by up regulating the TSP1 expression. TSP1 inhibited tristetraprolin (TTP) to prevent IL-10 mRNA decay in Br cells. Administration of VIP inhibited FA response through restoration of immune suppressive functions in Br cells. In conclusion, administration of VIP can alleviate FA response through up regulating expression of TSP1 to stabilize IL-10 expression in FA Br cells and recover the immune regulatory functions. The results have translational potential for the treatment of FA and other disorders associated with immune regulatory dysfunction of Br cells.

Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair.

Colorectal cancer (CRC) onset is profoundly affected by Western diet. Here, we report that high-fat (HF) diet-induced, organ-specific colonic lysine homocysteinylation (K-Hcy) increase might promote CRC onset by impeding DNA damage repair. HF chow induced elevated methionyl-tRNA synthetase (MARS) expression and K-Hcy levels and DNA damage accumulation in the mouse and rat colon, resulting in a phenotype identical to that of CRC tissues. Moreover, the increased copy number of MARS, whose protein product promotes K-Hcy, correlated with increased CRC risk in humans. Mechanistically, MARS preferentially bound to and modified ataxia-telangiectasia and Rad3-related protein (ATR), inhibited ATR and its downstream effectors checkpoint kinase-1 and p53, and relieved cell-cycle arrest and decreased DNA damage-induced apoptosis by disrupting the binding of ATR-interacting protein to ATR. Inhibiting K-Hcy by targeting MARS reversed these effects and suppressed oncogenic CRC cell growth. Our study reveals a mechanism of Western-diet-associated CRC and highlights an intervention approach for reversing diet-induced oncogenic effects.

Post-transcriptional regulation of interleukin-10 in peripheral B cells of airway allergy patients.

The dysfunction of peripheral immune tolerance plays an important role in the pathogenesis of allergic diseases. Recent reports indicate that micro RNA (miR)-98 is associated with the process of aberrant immune responses. This study aims to test a hypothesis that miR-98 is associated with the pathogenesis of airway allergy via interfering with the development of regulatory B cells (Breg). In this study, patients with airway allergy were recruited into this study. The frequency of Bregs was assessed by flow cytometry. The levels of miR-98 in peripheral B cells were determined by RT-qPCR. A cell-culture model of B cells was developed to test the role of miR-98 in the repressing of interleukin (IL)-10 in B cells. The results showed that the levels of IL-10 in peripheral B cells were significantly lower in patients with airway allergy as compared with healthy subjects. High levels of miR-98 (one of the miR-98 members) were detected in peripheral B cells of patients with airway allergy, which was mimicked by stimulating B cells with IL-4. Histone acetyltransferase p300 was involved in the IL-4-induced miR-98 expression. miR-98 mediated the IL-4-inhibited IL-10 expression in B cells. In conclusion, miR-98 affects the expression of IL-10 in B cells and may be a novel therapeutic target for the treatment of allergic diseases.

Staphylococcal enterotoxin B-derived haptens promote sensitization.

T helper 2 (Th2) polarization is a major pathological feature in allergic diseases; its etiology is not fully understood. This study aims to elucidate the adjuvant effect of the microbial product-derived small peptides in the initiation of antigen-specific Th2 polarization. In this study, a clinical survey of patients with chronic rhinosinusitis (CRS) and food allergy (FA) was carried out. The Staphylococcal enterotoxin B (SEB)-derived small peptides (Ssps) were examined in the human stool extracts. The formation of Ssp/antigen adducts was tested in a protein-protein combination assay. The bone marrow-derived dendritic cells (BMDCs) were employed to test the role of Ssp/ovalbumin (OVA) adducts in the dendritic cell (DC) maturation. A mouse model was developed to test the role of Ssp/OVA adducts in the initiation of Th2 polarization in the intestine. The results showed that 54 (18.2%) patients with FA were diagnosed among 296 patients with SEB(+) CRS; only eight (2.9%) FA patients were identified among 272 patients with SEB(-) CRS. Ssps were detected in the stool protein extracts from FA patients with SEB(+) CRS, but not in those with SEB(-) CRS. Ssp/OVA adducts induced DC maturation, speeded up DC migration, activated CD4(+) T cells in the regional lymph nodes and induced skewed Th2 polarization in the local tissue. We conclude that patients with SEB(+) CRS are prone to suffering from FA. SEB can be degraded to Ssps in the gastrointestinal tract. The Ssps can bind macromolecular antigens to form adducts to promote the antigenicity of the antigens and induction of the antigen-specific Th2 polarization and inflammation in the local tissue.

Integrin alphavbeta6 promotes tumor tolerance in colorectal cancer.

Tumor immune tolerance plays a critical role in tumor cell survival; the establishment of tumor immune tolerance is incompletely understood yet. Integrin alphavbeta6 (avb6) is involved in tumor growth and metastasis. This study aimed to observe the effect of avb6 on the development of tumor tolerance in colorectal cancer (CRC). In this study, 28 CRC patients were recruited. The frequencies of tolerogenic dendritic cells (TolDC), regulatory T cells (Treg), and CD8+ T cells in surgically removed CRC tissue were assessed by flow cytometry. The levels of avb6 in CRC tissue were measured by enzyme-linked immunoassay (ELISA). The effect of avb6 on inducing TolDCs and Tregs was evaluated with the cell culture model. The results showed that in surgically removed CRC tissue, we detected higher frequencies of TolDC and Tregs, lower frequency CD8+ T cells and high levels of avb6 as compared with non-CRC tissue. CRC protein extracts could induce TolDC development that could be blocked by anti-avb6 antibody. CRC-derived DCs could convert naïve CD4+ T cells to Tregs. Peripheral CD8+ T cells from CRC patients still retained the ability to produce granzyme B and to proliferate in response to CRC tumor antigen in culture that was abolished by the presence of CRC-derived Tregs. We conclude that CRC-derived avb6 is involved in the establishment of tumor immune tolerance in local tissues.

Interleukin (IL)-23 suppresses IL-10 in inflammatory bowel disease.

Interleukin (IL)-10 plays an important role in immune regulation in the intestine. Immune deregulation is suggested in the pathogenesis of inflammatory bowel disease (IBD). This study aims to elucidate the role of IL-23 in the suppression of IL-10 in the IBD intestinal mucosa. Surgically removed colon specimens were obtained from 16 IBD patients. The expressions of IL-10, IL-23, and IgA in the specimens were examined at the protein and gene transcriptional levels. The gene transcription of IL-10 was assessed by chromatin immunoprecipitation assay and promoter accessibility assay. The levels of IgA and IL-10 were significantly lower, whereas the levels of IL-23 were higher, in IBD specimens than in normal controls. The levels of IgA and IL-10 were negatively correlated with the infiltration of inflammatory cells in the IBD mucosa. The production of IL-10 by lamina propria mononuclear cells was lower in the IBD group than in the control group, and these levels could be enhanced by blocking IL-23. The gene transcription of IL-10 was significantly suppressed in CD4(+) T cells of IBD mucosa; this phenomenon could be replicated in vitro by adding IL-23 in the culture of polarized Th2 cells. Overexpression of IL-23 in the intestinal mucosa suppresses the production of IL-10, which weakens the defensive barrier by reducing the production of IgA in the gut.

Total synthesis of sphingofungin F based on chiral tricyclic iminolactone.

A new, efficient synthesis of sphingofungin F has been accomplished with 10.4% overall yield in 15 steps. The salient features of the synthesis are the utilization of methyl tricyclic iminolactone 3 for the asymmetric aldol reaction as a key step to introduce two desired stereogenic centers, one-pot reaction for the synthesis of omega-hydroxyketone from epsilon-caprolactone, and an effective one-step deprotection strategy to remove all protecting groups using 0.2 N HCl.

Immunoglobulin kappa and immunoglobulin lambda are required for expression of the anti-apoptotic molecule Bcl-xL in human colorectal cancer tissue.

OBJECTIVE: Aberrant expression of immunoglobulin (Ig) by cancer cells has been documented in a number of malignant tumors but its biological significance is unclear. Cancer cells overexpress anti-apoptotic molecules such as Bcl-xL. The present study aimed to examine the role of expression of Ig light-chain Igk and Iglambda in maintaining the high levels of Bcl-xL in colorectal cancer cells. MATERIAL AND METHODS: Thirty patients with colorectal cancer were recruited to this study. Expression of Igk, Iglambda and Bcl-xL in surgically removed cancer tissue was examined by immunohistochemistry and/or flow cytometry. Using the HT29 cell line as a study platform, RNA interference (RNAi) was employed to knock out the genes of Igk and Iglambda in the cancer cell line; the expression of Bcl-xL in HT29 cells was subsequently analyzed. RESULTS: Human colorectal cancer cells, but not normal colorectal tissue, expressed both Igk and Iglambda in the cytoplasm. High levels of Bcl-xL were detected in cancer cells. Using RNAi to knock out the genes of Igk and/or Iglambda, Bcl-xL expression in HT29 cells was significantly suppressed and the cells became apoptotic. CONCLUSION: The results suggest that expression of Igk and Iglambda is required to stabilize Bcl-xL expression in cancer cells.

[Detection and identification of specific serum biomarkers in papillary thyroid cancer].

OBJECTIVE: To detect and identify the potential specific serum biomarkers for diagnosis of papillary thyroid cancer. METHODS: Samples of 35 patients with papillary thyroid carcinoma, 40 patients with benign thyroid nodule and 34 healthy individuals were analyzed using the SELDI-TOF ProteinChip System and bioinfomation technology to find the differential peaks which were separated by HPLC and then further analyzed by LC-MS/MS. The protein sequences were analyzed by SEQUEST software and searched in Bioworks database. RESULTS: The top six mass-to-charge ratio (M/Z) peaks with the smallest P value were 6651, 6452, 7653, 7932, 15 106 and 15 848 Da, respectively. The 6651 and 6452 Da proteins were weakly expressed in papillary thyroid carcinoma but highly expressed in benign thyroid nodules and healthy individuals. The differences had statistical significance (P < 0.01). The 7653, 7932, 15 106, 15 848 Da proteins were highly expressed in papillary thyroid carcinoma but weakly expressed in benign thyroid nodules and healthy individuals. The differences were statistically significant (P < 0.01). Combination of these six proteins, using the method of leave-one-out to make crossing detection, the specificity of discriminating papillary thyroid carcinoma and non-cancer was 88.0%, and its sensitivity was 92.5%. The 6651 and 6452 Da proteins were identified as apolipoprotein C-I and apolipoprotein C-III, respectively. The 7653 and 15 106 Da proteins were identified as the same protein-alpha-globin, and the 7932 and 15,848 Da proteins were identified as the same protein-beta-globin. CONCLUSION: The detection of differentially expressed apolipoprotein C-I, apolipoprotein C-III, alpha-globin, and beta-globin may have utility for diagnosis of papillary thyroid carcinoma and are worthy of further investigation.

[Screening and identification analysis of serum protein biomarkers in nephroblastoma].

OBJECTIVE: To screen and characterize the serum protein biomarkers in nephroblastoma so as to establish the proteins as the specific serum biomarkers for diagnosis and prognosis monitoring. METHODS: The differential protein peaks were located by detecting serum samples of preoperative and postoperative patients and normal children using the SELDI-TOF MS technology. After purification, the differential proteins were further analyzed by LC-MS/MS and the protein sequences searched in database. RESULTS: Two peaks with m/z of 6455.5 and 6984.4 were selected as potential biomarkers. They were weakly expressed in nephroblastoma (intensity: 1029 +/- 364, 297 +/- 126) but highly expressed in normal individuals (2108 +/- 837, 753 +/- 226); another peak with m/z of 9190.8 was weakly expressed in preoperative sera (283 +/- 154) but highly expressed in serum samples of postoperative patients and normal children (5974 +/- 657, 6231 +/- 519). The protein at 6455.5 and 9190.8 were identified as apolipoprotein C-III and haptoglobin respectively. CONCLUSION: The detection of differentially expressed apolipoprotein C-III and haptoglobin may have potential utilities for serum diagnosis, malignancy classification and prognosis monitoring of nephroblastoma and is worthy of further studies and applications.

Diastereo- and enantioselective synthesis of beta-hydroxy-alpha-amino acids: application to the synthesis of a key intermediate for lactacystin.

The development of a highly efficient and stereoselective methodology for the preparation of beta-hydroxy-alpha-amino acids is described. Nucleophilic addition of enolates of tricyclic iminolactones 1a and 1b to aldehydes in the presence of 6 equiv of lithium chloride in THF at -78 degrees C leads to aldol adducts in good yield (63-86%) and high diastereoselectivity (up to >25:1 dr). Subsequently, hydrolysis of the aldol adducts under acidic conditions leads to the corresponding beta-hydroxy-alpha-amino acids in good yields (up to 83%) and excellent enantiomeric excesses (99% ee) with good recovery yields of the chiral auxiliaries 6 and 7. This methodology was applied to the facile synthesis of the key intermediate for lactacystin along with several isomers.

[The tendency of physiological and psychological change of the armored vehicle drivers working continuously in hot environment].

OBJECTIVE: To probe the tendency of physiological and psychological change of armored vehicle drivers working continuously in hot environment. METHODS: Ten cross-designed standard subjects were divided into control group and driver group. The driver group worked continuously in 32 degrees C approximately 38 degrees C and RH 50% approximately 80% environment. Heart rate, body temperature, systolic blood pressure and pulse pressure were synchronously and dynamically determined during work. Psychological parameters such as profile of mood states (POMS) questionnaire, serial addition/subtraction (SAS) and two-digit search (TDS) selected from neurobehavioral evaluation system (NES) before and after work were also tested. RESULTS: The curves of the four main physiological parameters rapidly synchro-rose to a peak at (36 +/- 3) min, whereafter the curves descended smoothly. At (144 +/- 8) min, the curves climbed up to the second peak. The determination of the behavioral psychology revealed that the degree of fatigue of the drivers increased gradually when the working time prolonged, and the grip descended by great extent, excitement reduced markedly after work, but the negative mood, such as confusion and depression were increased, error of visual apperceive-operation was increased, right decreased, intelligence reduced, rapidity and delicacy of movement reduced. CONCLUSION: The physiological parameters of armored vehicle drivers working continuously in the hot condition appeared double-peak effect, the 1st peak was at (36 +/- 3) min, and the body was in mobilizing stage. Whereafter, the body was in smooth stage. And at (144 +/- 8) min, when the 2nd peak appeared, the body then was in physiological tolerance limit stage.

[Gene expression profile of human adenocarcinoma by cDNA microarray and clustering].

OBJECTIVE: To investigate the gene expression profile of human gastric adenocarcinoma by means of cDNA microarray and to analyze its biological significance. METHODS: Paired tumor and non-tumor specimens from 18 cases of advanced gastric adenocarcinoma were studied. Total RNA was isolated and labeled by reverse transcription reaction with cy5 and cy3 for cDNA probe. cDNA microarrays containing 148 genes were hybridized with labeled cDNA probe. Data from cDNA microarray experiments were analyzed by average-linkage hierarchical clustering and significance analysis of microarrays (SAM). RESULTS: Eighteen tumor and non-tumor specimens were clearly divided by clustering analysis. Three features of gene expression profile were found in gastric adenocarcinoma and non-tumor tissues. The profile of differential gene expression in tumor and non-tumor tissues was mainly shown in feature B and feature C. In gastric adenocarcinoma tissues, the expression of genes in feature B was lower and that in feature C was higher. The profile of differential gene expression among gastric adenocarcinoma tissues was found in feature A. In feature A, the profile of similar gene expression was found in paired tumor and non-tumor tissues from 13 patients. SAM analysis showed that 19 genes in feature B and 12 genes in feature C were of significant difference between tumor and non-tumor specimens. The expression levels of genes related to cell cycle, growth factor, cell adhesion, and matrix remodeling were higher or lower in gastric adenocarcinoma tissues. CONCLUSION: Data from cDNA microarray experiments can clearly distinguish gastric adenocarcinoma from non-tumor tissues. The profiles show that gene expression in gastric adenocarcinomas is both homogeneous and heterogeneous. The homogeneous gene expression profile is found in both tumor and non-tumor tissues from 13 patients, suggesting that some gene aberrance is an early event of carcinogenesis of gastric adenocarcinoma. This study provides not only a new molecular basis for understanding biological properties of gastric adenocarcinoma, but also useful resources for future development of diagnostic and prognostic markers for gastric adenocarcinoma.