Background::Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods::Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results::Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). Conclusions::ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Ganoderma ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/genetics*

Betacoronavirus ; genetics ; Coronavirus Infections ; diagnosis ; Fluorescence ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; Polymerase Chain Reaction ; methods

AIM:To observe the pathological changes of the lower segment of nasolacrimal duct mucosa in rabbits at different stages after retrograde lachrymal dilated drainage tube implantation.
METHODS:Totally 14 New Zealand rabbits were used in the present study. One side of nasolacrimal duct was obstructed to produce an experimental model and operated the reverse implantation of nasolacrimal duct intubation. Histological changes of the lower segment of nasolacrimal duct mucosa were observed by routine light microscope at 2, 4, 6, 8, 10, 12 and 14wk after the operation.
RESULTS: Compared with the control side, the group of 2 and 4wk after surgery presented the inflammatory cytokine. The group of 12wk after the operation presented isolated granuloma. Group 12 and 14wk presented scattered granuloma. The size of the granulomas was smaller and the density of epithelioid cell and fibroblast were lower in group 12wk than those in group 14wk by HE and Masson trichrome stain.
CONCLUSION:Recurrent Silicone Tube is used to treat nasolacrymal duct obstruction. Nasolacrimal duct can be narrowed and blocked again by granuloma, progressive fibrosis and adhesion of surrounding tissues when tube is in the duct more than 12wk.

BACKGROUNDThe enlarged prostate leads to obstruction and lower urinary tract symptoms (LUTS), which comprise frequency, urgency, weak stream, straining and nocturia. This study was conducted in a large series of patients to evaluate the relationship between LUTS as stipulated in the International Prostate Symptom Score (IPSS) and the objective parameters related to benign prostatic hyperplasia (BPH).

METHODSWe enrolled 1295 BPH patients from seven centers. The patients were either at first diagnosis of BPH or had discontinued medical treatment for at least 3 months. Those with several other diseases that may be potential risk factors affecting urinary symptoms were excluded from the study. Age, IPSS, prostate volume, peak flow rate, urine volume and post-voiding residual urine volume were measured. The relationship between IPSS and objective parameters were quantified by means of Spearman correlation coefficients. The differences in these parameters between the groups with mild, moderate or severe symptoms were also evaluated.

RESULTSStatistically significant correlations were found between IPSS and objective parameters by means of Spearman correlation coefficients. When the patients were divided into three groups with different severities of symptoms, there were significant differences in peak flow rate, urine volume, prostate volume, residue urine volume and quality of life, whereas average age and prostate-specific antigen levels were similar. However, there was evident overlap of these parameters between the groups. The same results were found when the irritative or obstructive subscore of IPSS was considered.

CONCLUSIONSThe correlation between objective parameters of BPH and LUTS is significant. However, it is hard to predict the severity of symptoms by these parameters.

Aged ; Aged, 80 and over ; Humans ; Male ; Middle Aged ; Prostatic Hyperplasia ; diagnosis ; psychology ; Quality of Life ; Urination Disorders ; etiology

OBJECTIVETo investigate the CT and MRI manifestatitions of intraductal papillary mucinous neoplasm (IPMN) of the pancreas.

METHODSBoth clinical and imaging data of 12 pathologically confirmed intraductal papillary mucinous neoplasm, of the pancreas were retrospectively analyzed.

RESULTSThe pancreatic IPMN can be classified into two types based on CT image: the branch duct IPMN (n=7) originated from the head and uncinate process of the pancreas. The tumor consisted of lobulated or clustered small cyst lesions with septa among them, the wall and septa can be enhanced; the combined IPMN (n=5) involved branch ducts of the uncinate process as well as the main pancreatic ducts with dilatation (diameter: 4-7 mm), one of these involved the branch ducts along the pancreatic body. The pancreatic IPMN was mainly found in elderly patient with a chief clinical symptoms of abdominal pain and/or pancreatitis.

CONCLUSIONThe intraductal papillary mucinous neoplasm of the pancreas enjoys specific features in CT and MRI image, which are helpful to the diagnosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal ; diagnosis ; diagnostic imaging ; Carcinoma, Papillary ; diagnosis ; diagnostic imaging ; Cystadenocarcinoma, Mucinous ; diagnosis ; diagnostic imaging ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pancreatic Ducts ; diagnostic imaging ; pathology ; Pancreatic Neoplasms ; diagnosis ; diagnostic imaging ; Retrospective Studies ; Sensitivity and Specificity ; Tomography, X-Ray Computed

OBJECTIVETo investigate the expression of OPCML gene in ovarian epithelial carcinoma and determine the relationship between mRNA expression and methylation of their promoters.

METHODTwenty normal ovarian tissues and 89 ovarian epithelial tumor specimens (72 malignant, 17 benign), as well as 3 ovarian carcinoma cell lines (SKOV-3, CAOV3, and 3AO), were collected for detection of OPCML gene expression by reverse transcription-polymerase chain reaction and for detection of promoter methylation by restriction enzyme cut analysis from 7. 1999 to 7. 2003.

RESULTSAmong ovarian epithelial carcinoma 19.4% expressed OPCML mRNA, while 85% of normal ovarian tissue and 76.5% of benign ovarian tumor. The ratio of expression of OPCML mRNA in ovarian epithelial carcinoma was significantly lower than those of normal (chi2 = 30.108, P = 0.0000) and benign tumors (chi2 = 21.162, P = 0.000). No OPCML mRNA expression was found in SKOV-3 and CAOV3, but was found in 3AO. Methylations were detected in 44.4% of cancer cells promoter, while 0% in normal ovarian tissue and benign ovarian tumors. The ratio of methylation of ovarian epithelial carcinoma was significantly higher than those of normal (chi2 = 13.630, P = 0.0000) and benign tumors (chi2 = 11.797, P = 0.000). Methylation was found in SKOV-3 and CAOV3, but not in 3AO. The relationship between gene expression and promoter methylation was correlated (r = 11.589, P = 0.002), especially at Hap I1 site (r = 11.640, P = 0.004). Methylation was also found in SKOV-3 and CAOV3 cell lines, but not in 3AO cell line.

CONCLUSIONDeletion of OPCML gene exists in ovarian epithelial carcinoma cell. The gene promoter methylations, especially Hap II motif, may be one of pathways that contribute the inhibition of OPCML expression.

Adult ; Aged ; Cell Adhesion Molecules ; genetics ; Cell Line, Tumor ; CpG Islands ; genetics ; DNA Methylation ; Female ; GPI-Linked Proteins ; Gene Deletion ; Humans ; Middle Aged ; Ovarian Neoplasms ; genetics ; pathology ; Promoter Regions, Genetic ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo study the changes of IL-12 produced by dendritic cells in peripheral blood in children with Henoch-Schonlein purpura (HSP), and to explore its influence on TH1/TH2 balance in order to elucidate its significance in the pathogenesis of HSP.

METHODSThe levels of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and interleukin-12 (IL-12) in plasma were determined by ELISA in 60 HSP children (HSP group) and 21 healthy children (Control group). Peripheral blood mononuclear cells (PBMC) of 22 HSP patients and 21 healthy children were cultured in vitro and then were transformed into dendritic cells. The levels of IL-12 in the supernatant were detected by ELISA and the positive expression rate of CD1a(+) was detected by indirect immunofluorescence procedure.

RESULTS1) The levels of IFN-gamma and the ratio of IFN-gamma/IL-4 in plasma of the HSP group were lower than those of the Control group (IFN-gamma 30.59 +/- 11.27 pg/mL vs 43.38 +/- 19.19 pg/mL; IFN-gamma/IL-4 ratio 0.70 +/- 0.28 vs 1.33 +/- 0.57) (P < 0.01). The levels of IL-12 in the HSP group were also lower than those of the Control group (153.95 +/- 91.88 pg/mL vs 323.06 +/- 162.34 pg/mL; P < 0.01). In contrast, the levels of IL-4 were higher than those of the Control group (45.08 +/- 9.19 pg/mL vs 32.95 +/- 7.10 pg/mL; P < 0.01). The plasma levels of IL-12 positively correlated with the IFN-gamma levels (r=0.52, P < 0.01) and the ratio of IFN-gamma/IL-4 (r=0.43, P < 0.01) in the HSP group. 2) The IL-12 levels in the supernatant of the HSP group were lower than those of the Control group (357.06 +/- 153.56 pg/mL vs 489.80 +/- 213.45 pg/mL; P < 0.05), and had a positive correlation with the plasma IL-12 levels (r=0.74, P < 0.01). 3) The positive expression rate of CD1a(+) of the HSP group was lower than that of the Control group [(27.42 +/- 10.75)% vs (35.68 +/- 12.18)%; P < 0.05], and positively correlated with the IL-12 levels in the supernatants (r=0.57, P < 0.01) and in plasma (r=0.68, P < 0.01).

CONCLUSIONSThere was an imbalance of TH1/TH2 in HSP children. The decrease of TH1 function had a positive correlation with the low levels of IL-12 in plasma, while the latter correlated closely with decreased number and / or function of dendritic cells, suggesting that the decreased number and / or function of dendritic cells in peripheral blood resulted in the imbalance of TH1/TH2 indirectly.

Adolescent ; Antigens, CD1 ; analysis ; Cells, Cultured ; Child ; Child, Preschool ; Dendritic Cells ; immunology ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-12 ; biosynthesis ; blood ; Interleukin-4 ; blood ; Male ; Purpura, Schoenlein-Henoch ; immunology ; Th1 Cells ; immunology ; Th2 Cells ; immunology

OBJECTIVETo study the expressions of VEGF/VEGFRs and activation of STATs in ovarian epithelial carcinoma, and to elucidate direct effect of VEGF on ovarian carcinoma cells.

METHODSTissue samples from 42 women with primary ovarian epithelial carcinoma (OVCA), 29 with begnin ovarian tumor (OVBT) and 11 with normal ovarian tissue (NOV) were collected. LSAB immunohistochemical staining was used to determine the expression of VEGF, VEGFR1, VEGFR2 and activated STATS (P-STAT1, P-STAT3, P-STAT5, P-STAT6) proteins.

RESULTS(1) Semi-quantitative scoring showed that VEGF expression in OVCA was significantly higher than that in OVBT and NOV (P < 0.01). Expressions of VEGFR1 and VEGFR2 were significantly elevated in OVCA, including tumor cells and stromal vascular endothelial cells (P < 0.01, compared with OVBT and NOV). There was no difference in VEGFRs expressions between OVBT and NOV. (2) In OVCA, tumor cells and endothelial cells expressed P-STAT3 and P-STAT5 at significantly higher levels than those in OVBT and NOV (P = 0.000). The staining of P-STAT1 and P-STAT6 was weak with no significant differences among OVCA, OVBT and NOV. (3) Expressions of VEGFR1 and VEGFR2 in endothelial cells were significantly correlated with P-STAT5 and P-STAT3, respectively (P = 0.006 and 0.001). In cancer cells, VEGF, VEGFR1 and VEGFR2 were all significantly correlated with P-STAT3 and P-STAT5 (P = 0.000), but not with P-STAT1 or P-STAT6.

CONCLUSIONVEGF affects ovarian carcinoma cells via VEGFRs, and STATs probably participate in intracellular signaling of VEGF.

Adult ; Aged ; Cystadenocarcinoma, Mucinous ; metabolism ; pathology ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Cystadenoma, Mucinous ; metabolism ; pathology ; Cystadenoma, Serous ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Endothelial Cells ; metabolism ; Female ; Humans ; Middle Aged ; Milk Proteins ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Ovary ; metabolism ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Signal Transduction ; Trans-Activators ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism