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.

HDAC9 inhibition reduces skeletal muscle atrophy and enhances regeneration in mice with cigarette smoke-induced COPD.

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD), and sarcopenia is one of the significant comorbidities of COPD. However, the pathogenesis of CS-related deficient skeletal muscle regeneration has yet to be clarified. The impact of CS on myoblast differentiation was examined, and then we determined which HDAC influenced the myogenic process and muscle atrophy in vitro and in vivo. Finally, we further investigated the potential mechanisms via RNA sequencing. Long-term CS exposure activated skeletal muscle primary satellite cells (SCs) while inhibiting differentiation, and defective myogenesis was also observed in C2C12 cells treated with CS extract (CSE). The level of HDAC9 changed in vitro and in vivo in CS exposure models as well as COPD patients, as detected by bioinformatics analysis. Our data showed that CSE impaired myogenic capacity and myotube formation in C2C12 cells via HDAC9. Moreover, inhibition of HDAC9 in mice exposed to CS prevented skeletal muscle dysfunction and promoted SC differentiation. The results of RNA-Seq analysis and verification indicated that HDAC9 knockout improved muscle differentiation in CS-exposed mice, probably by acting on the AKT/mTOR pathway and inhibiting the P53/P21 pathway. More importantly, the serum of HDAC9 KO mice exposed to CS alleviated the differentiation impairment of C2C12 cells caused by serum intervention in CS-exposed mice, and this effect was inhibited by LY294002 (an AKT/mTOR pathway inhibitor). These results suggest that HDAC9 plays an essential role in the defective regeneration induced by chronic exposure to CS.

Clinical Characteristics and Interventions for Ingested Magnetic Foreign Bodies in Children: A Systematic Review and Meta-analysis.

BACKGROUND: Ingested foreign materials are a common cause for hospital emergency department visit. Foreign objects such as magnets found in the gastrointestinal tract can cause serious problem because magnets attract to each other across the intestinal wall, often resulting in severe damage. We aimed to review the magnitude of the problem, the clinical characteristics and the interventions related to this problem. METHODS: A systematic review and meta-analysis of the retrospective studies published in PUBMED, MEDLINE, Web of Science, Embase and Cochrane was conducted. The search was limited to studies published from Jan 1, 2000 to July 31, 2022, with the last search done on August 1, 2022. No publication restrictions or study design filters were applied. RESULTS: Data from 24 retrospective cohort studies with 2014 patients were included in the review. 63.6% (95% CI 59.9%-67.3%) of children who had swallowed foreign bodies were male, and 43% (95% CI 29.3%-57.3%) children presented with non-specific symptoms or had a complete absence of symptoms. Only 74.7% (95% CI 58.7%-88%) of the children has clear history of ingested foreign bodies. Abdominal surgery was the most prevalent interventions (43.3%, 95%CI 32.5%-54.1%) among the inpatients, while conservative treatments were the second common intervention (40.3%, 95%CI 27.8%-52.9%) among the inpatients and outpatients. Intestinal perforation or fistula occurred in 30.2% (95%CI 22.5%-37.8%) children. CONCLUSION: Despite significant heterogeneity among primary studies, our results detail the morbidity, clinical characteristics and interventions associated with ingested magnetic foreign bodies in children.

Prognostic significance of circulating Epstein-Barr virus DNA in pulmonary lymphoepithelioma-like carcinoma: A meta-analysis and validation study.

In small-scale studies, circulating Epstein-Barr virus (EBV) DNA levels have prognostic value in patients with pulmonary lymphoepithelioma-like carcinoma (LELC). Therefore, we performed a comprehensive meta-analysis to evaluate the prognostic significance of circulating EBV DNA levels in patients with pulmonary LELC. Studies that discussed the prognostic significance of circulating EBV DNA detection in pulmonary LELC were eligible for inclusion in this study. The overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Pooled hazard ratio (HR), 95% confidence intervals (CIs), and p value were calculated to estimate the prognostic significance of EBV DNA levels. Additionally, we conducted a further observation using an independent cohort. The pooled HR and 95% CI of pretreatment EBV DNA levels for OS and PFS were 3.63 (95% CI: 2.90-4.55) and 2.88 (95% CI: 1.90-4.38), respectively. The pooled HR and 95% CI for Posttreatment EBV DNA levels for OS and PFS were 3.77 (95% CI: 2.96-4.80) and 3.52 (95% CI: 1.91-6.51, p < 0.001), respectively. The independent cohort showed similar results that patients with high pretreatment EBV DNA or positive posttreatment EBV DNA had significantly inferior PFS. Circulating EBV DNA levels provide prognostic values of survival and treatment response in pulmonary LELC patients.

Clinical Characteristics and Management of Colorectal Vascular Malformation in Children: A Retrospective Study of 23 Cases.

INTRODUCTION: The objective of this study is to summarize the clinical characteristics and management of rare diseases of colorectal vascular malformation (CRVM) in children. METHODS: We retrospectively analyzed the clinical data of CRVM patients admitted to the Children's Hospital of Fudan University from 2004 to 2019. RESULTS: A total of 23 cases (16 males, 7 females) were enrolled. The median age of symptom onset was 1.4 years. Hematochezia and anemia were cardinal symptoms. Fourteen patients (60.9%) were misdiagnosed as anal fissures (n = 4), internal hemorrhoids (n = 3), rectal polyps (n = 2), inflammatory bowel disease (n = 2), portal hypertension (n = 2), and Meckel's diverticulum (n = 1), respectively. The average time from symptom onset to diagnosis was 4.5 ± 4.4 years. Other vascular malformations were detected in eight patients (34.8%). All patients showed a positive anomalous vascular image on contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI). The sensitivity of colonoscopy in the diagnosis of CRVM was 82.6% (19/23). A total of 21 patients underwent a modified Soave procedure. The lesions were mostly restricted to the colorectum and showed transmural diffuse distribution, with an average length of 20 ± 5.4 cm. Two patients (9.5%) experienced surgical complications. Bloody stools reappeared in two patients (9.5%), and colonoscopy showed abnormal angiogenesis at the anastomotic site, which were cured by sclerotherapy and/or electrocautery. The median follow-up time was 78 months. Bloody stools were absent at the last time of follow-up, and hemoglobin was in the normal range for all patients. CONCLUSION: The identification of CRVM in children often is delayed. Colonoscopy, CT, and MRI are essential in making the correct diagnosis. The modified Soave procedure is safe and feasible to treat CRVM in children. Endoscopic sclerotherapy and/or electrocautery can be used for residual lesions.

Outcomes and comparations of pediatric surgery about choledochal cyst with robot-assisted procedures, laparoscopic procedures, and open procedures: A meta-analysis.

Background: Choledochal cysts (CC) are rare disorders characterized by congenital biliary dilatation of the intrahepatic or extrahepatic bile ducts and always relate to pancreaticobiliary maljunction. Robot-assisted surgery has been able to complete almost all pediatric endoscopic surgery nowadays. But evidence of the post-operative outcomes of robotic-assisted operation is limited, comparing with the laparoscopic operation and traditional open operation. The aim of this meta-analysis was to identify the advantages and deficiencies about robotic-assisted operation for CC. Methods: A meta-analysis of retrospective studies published in PUBMED, MEDLINE, Web of Science and China National Knowledge Infrastructure (CNKI). No date limit was used, with the last search on April 30, 2022. No publication restrictions or study design filters were applied. Results: Nine retrospective cohort studies with 1,395 patients [366 in the robotic-assisted operation group (RG), 532 in the laparoscopic operation group (LG) and 497 in the open operation group (OG)] were enrolled in our study. Subgroup analysis demonstrated the RG had significant longer operative time [standardized mean difference (SMD) = 1.59, 95% CI = (0.02, 3.16), P < 0.05], less blood loss [SMD = -1.52, 95% CI = (-2.71, -0.32), P < 0.05], shorter enteral feeding time [SMD = -0.83, 95% CI = (-1.22, -0.44), P < 0.001], shorter time to stay in the hospital [SMD = -0.81, 95% CI = (-1.23, -0.38), P < 0.001], fewer post-operative complications [Relative risk (RR) =1.09, 95% CI = (1.04, 1.13), P < 0.001] but higher expenses [SMD = 8.58, 95% CI = (5.27, 11.89), P < 0.001] than LG. While a significant older age [SMD = 0.46, 95% CI = (0.26, 0.66), P < 0.001], longer operative time [SMD = 3.96, 95% CI = (2.38, 5.55), P < 0.001] and shorter time to stay in the hospital [SMD = -0.93, 95% CI = (-1.62, -0.25), P < 0.05] than OG. Conclusions: Laparoscopic and robotic-assisted procedure are both safe and minimal invasive operational strategies. Robotic-assisted procedure may slowly surpass and has a trend to replace laparoscopy for its advantages. More experiences in robotic-assisted operation should be accumulated for the unexpected complexities, so as to be more stable in the younger age of children.

Comprehensive Liquid Profiling of Circulating Tumor DNA and Protein Biomarkers in Long-Term Follow-Up Patients with Hepatocellular Carcinoma.

PURPOSE: Circulating tumor DNA (ctDNA) provides a novel approach for detecting tumor burden and predicting clinical outcomes of hepatocellular carcinoma (HCC). Here, we performed a thorough evaluation of HCC circulating genetic features and further fully integrated them to build a robust strategy for HCC monitoring and prognostic outcome assessment. EXPERIMENTAL DESIGN: We performed target sequencing and low-coverage whole-genome sequencing on plasma samples collected from 34 long-term follow-up patients with HCC to capture tumor somatic SNVs and CNVs, respectively. Clinical information was also obtained to evaluate the prognostic performance of ctDNA comparing with clinically applied protein biomarkers. RESULTS: All plasma samples before surgery showed somatic genetic variations resembling corresponding tumor tissues. During follow-up, SNVs and CNVs dynamically changed correlating to patients' tumor burden. We integrated the comprehensive ctDNA mutation profiles to provide a robust strategy to accurately assess patients' tumor burden with high consistence comparing with imaging results. This strategy could discover tumor occurrence in advance of imaging for an average of 4.6 months, and showed superior performance than serum biomarkers AFP, AFP-L3%, and Des-Gamma-Carboxy Prothrombin (DCP). Furthermore, our strategy could precisely detect minimal residual disease (MRD) in advance and predict patients' prognostic outcomes for both relapse-free survival (P = 0.001) and overall survival (P = 0.001); further combining ctDNA with DCP could increase the sensitivity for MRD detection. CONCLUSIONS: We demonstrated that plasma CNV and SNV levels dynamically correlated with patients' tumor burden in HCC. Our strategy of comprehensive mutation profile integration could accurately and better evaluate patients' prognostic risk and detect tumor occurrence in advance than traditional strategies.

FGG promotes migration and invasion in hepatocellular carcinoma cells through activating epithelial to mesenchymal transition.

PURPOSE: The aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression. METHODS: The expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells. RESULTS: The expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1. CONCLUSION: FGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients.

Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in hepatocellular carcinoma.

Circular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNA related to HCC progression. A total of 42 dysregulated circRNA (38 down-regulated and 4 up-regulated) were identified in HCC tumor tissues compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC. CircADAMTS13, derived from Exon 13-14 of the ADAMTS13 gene, was significantly downregulated in HCC tumor tissues. Furthermore, clinicopathological analysis revealed that up-regulation of circADAMTS13 was negatively associated with tumor size but positively associated with prognosis. In addition, overexpression of circADAMTS13 could markedly inhibit HCC cell proliferation in vitro. Bioinformatic analysis and luciferase reporter assays further revealed that circADAMTS13 directly interacts with microRNA (miR)-484. Rescue experiments showed that miR-484 mimics can reverse the tumor-suppressing roles of circADAMTS13 in HCC. Therefore, our results demonstrated that circADAMTS13 can serve as a tumor suppressor during HCC progression via the functional pathway of sponging miR-484.

Evaluation and prediction of hepatocellular carcinoma prognosis based on molecular classification.

PURPOSE: Prediction of hepatocellular carcinoma (HCC) prognosis faced great difficulty due to tumor heterogeneity. We aimed to identify the prognosis-associated molecular subtypes existing in HCC patients and construct an evaluation model based on identified molecular classification. MATERIALS AND METHODS: Non-negative matrix factorization consensus clustering was performed using 371 HCC patients from The Cancer Genome Atlas (TCGA) to identify molecular subtypes, based on the expression profile of the survival-associated genes. Signature genes for different subtypes were identified by Significance Analysis of Microarray and Prediction Analysis for Microarrays. Model for subtype discrimination and prognosis evaluation was established using binary logistic regression. The model and its clinical implications were further validated in GSE5436 cohort and Fujian cohort. RESULTS: Based on TCGA data, we observed two molecular subtypes with distinct clinical outcomes including significantly different overall survival, tumor differentiation, TNM stage, and vascular invasion (all P<0.05). The existence of these two molecular subtypes was further validated in five other Gene Expression Omnibus datasets. Furthermore, we constructed an evaluation model based on six subtype signature genes, which can discriminate different subtypes with the cutoff of 0.385. Meanwhile, both Cox regression analysis and stratification analysis showed that the calculated continuous prognostic value could also effectively indicate HCC prognosis, regardless of patients' clinical conditions. The prognostic evaluation model was successfully validated in GSE54236 cohort and Fujian cohort. CONCLUSION: Two prognostic molecular subtypes existed among HCC patients, which provided promising strategies for overcoming HCC heterogeneity and could be utilized in future clinical application for predicting HCC prognosis.

Polydopamine-assisted versatile modification of a nucleic acid probe for intracellular microRNA imaging and enhanced photothermal therapy.

MicroRNAs play an important role in various biological processes, and their aberrant expression is closely associated with various human diseases, especially cancer. Real-time monitoring of microRNAs in living cells may help us to understand their role in cellular processes, which can further provide a basis for diagnosis and treatment. In this study, polydopamine was used to assist the versatile modification of a nucleic acid probe for intracellular microRNA imaging and enhanced photothermal therapy. Polydopamine can be covalently linked with a thiol-terminated nucleic acid probe through the Michael addition reaction under slightly alkaline conditions. This modification is mild and can be performed directly in an aqueous solution, which can better resist hydrolysis than the traditional modification processes, resulting in a nanoprobe with better stability and higher loading of nucleic acids. This prepared nanoprobe can easily enter cells without transfection agents and then realize the imaging of intracellular miRNA through fluorescence restoration. Moreover, the coating of PDA can enhance the photothermal conversion efficiency of the nanoprobe, making it suitable for photothermal therapy of cancer. It is expected that the PDA-based versatile modification can help to construct a promising platform for tumor imaging and treatment.

Assessment of corneal biomechanical behavior under posterior and anterior pressure.

PURPOSE: To determine the biomechanical response of the rabbit cornea to inflation under posterior and anterior pressure. METHODS: Twelve Japanese white rabbits were included in the study. A randomly selected eye from each animal was subjected to posterior pressure in an inflation test rig, and the other eye was subjected to anterior pressure after manually reversing its curvature. Specimens were loaded by cycles of pressure up to 40 mmHg, and the experimentally obtained pressure-deformation data were used to derive the stress-strain behavior of each eye using an inverse modeling procedure. RESULTS: The differences between the two groups in corneal thickness, diameter, and intraocular pressure (IOP) were not statistically significant (P=.935, .879 and .368, respectively). Corneas tested under posterior pressure displayed significantly higher stiffness (as measured by the tangent modulus) than those inflated by anterior pressure (P<.001). CONCLUSIONS: Cornea is a nonlinear viscoelastic tissue that presents different mechanical properties when tested under posterior and anterior pressure. The determination of the behavior under both forms of pressure could contribute to the construction of accurate finite element simulations of corneal behavior and the correction of tonometric IOP measurements. The difference in mechanical behavior between anteriorly and posteriorly loaded corneas in the study, although significant, could have been partly affected by the changes in microstructure possibly caused by changing corneal form to enable anterior loading.

Effects of repeated injection of kisspeptin-10 on the initiation of egg-laying in juvenile quail.

The kisspeptin (Kp) signaling pathway plays an essential role in the onset of reproduction in mammals. To investigate the effects of Kp on the initiation of egg laying in birds, juvenile female quail were given daily intraperitoneal injections of 300µl saline (control, Con), or 10nmol (low dosage, L) or 100nmol (high dosage, H) kisspeptin-10 (Kp-10) dissolved in 300µl saline for 3 weeks. The ratio of egg laying of quail in the L and H groups was notably increased compared to that of the Con group (P<0.01), which paralleled earlier ovarian growth and increases in circulating estrogen (E(2)) concentrations. In the hypothalamus, gonadotropin-releasing hormone-I (GnRH-I) mRNA expression was markedly up-regulated, whereas the level of gonadotropin-inhibiting hormone mRNA was down-regulated by high-dose Kp-10 (P<0.05). In the pituitary gland, expression of GnRH receptor type II, but not type I mRNA was significantly up-regulated by high-dose Kp-10 administration (P<0.05). Moreover, compared with the Con group, follicle-stimulating hormone (FSH) gene expression in the pituitary was significantly decreased in the L and H groups (P<0.05), whereas luteinizing hormone (LH) mRNA expression was significantly increased in the H, but not the L group (P<0.05). These results indicate that repeated peripheral Kp-10 injections can advance the sexual maturation of female quail by regulating the activities of the hypothalamus-pituitary-gonadal axis.

Effects of kisspeptin-10 on progesterone secretion in cultured chicken ovarian granulosa cells from preovulatory (F1-F3) follicles.

The effect of kisspeptin-10 (Kp-10) on the secretion of progesterone (P(4)) was investigated in cultured granulosa cells from F(1) to F(3) follicles of hens. The results showed that granulosa cells were stained with clear signals for kisspeptin using immunocytochemistry with the specific antibody against Kp-10. Among 10, 100 and 1000 nM concentrations tested, 100 nM Kp-10 treated for 24h significantly increased P(4) secretion in granulosa cells from F(1) to F(3) follicles. After 24h and 48 h of treatment, 100 nM Kp-10 showed a significant increase in P(4) secretion, while after 72 h of treatment P(4) secretion was markedly decreased by Kp-10 compared to the control group (P<0.05). F(1) and F(2/3) cells treated with 100 nM Kp-10 for 24h showed significantly increased viability (P<0.05) and which was in parallel to a marked increase in P(4) secretion (P<0.01). Real-time PCR results showed that the gene expression of the steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450scc) and the enzyme 3ß-hydroxysteroid dehydrogenase (3ß-HSD) in F(1) and F(2/3) granulosa cells was significantly up-regulated by 24h-100 nM Kp-10 treatment (P<0.05 versus P<0.01, respectively). However, there was no significant difference in StAR, P450scc and 3ß-HSD protein content between control and the Kp-10 treated group (P>0.05). These results indicate that Kp-10 stimulates P(4) secretion in cultured chicken granulosa cells, which was associated with an up-regulation in StAR, P450scc and 3ß-HSD gene transcription.