Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility.

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.

A structural equation model-based study on the status and influencing factors of acute exacerbation readmission of elderly patients with chronic obstructive pulmonary disease within 30 days.

OBJECTIVE: To investigate the circumstances that lead to acute exacerbation readmission of elderly patients with chronic obstructive pulmonary disease (COPD) within 30 days and to explore the influencing factors of readmission using a structural equation model to provide evidence for medical staff so that effective intervention measures can be taken. METHODS: The convenience sampling method was used to select 1120 elderly patients with COPD from the respiratory departments of thirteen general hospitals in the Ningxia region, China, from April 2019 to August 2020, who then completed a survey questionnaire. The survey questionnaire contained a general data questionnaire and the modified Medical Research Council, activities of daily living, geriatric depression scale and COPD assessment test scales. RESULTS: The readmission rate of patients with COPD presenting with acute exacerbation within 30 days was determined to be 21.52%. Therefore, the modified model measures data accurately. The results showed that seasonal factors, family rehabilitation, age factors and overall health status were direct factors in the acute exacerbation readmission of patients with COPD within 30 days of hospital discharge. Smoking is not only a direct factor for acute exacerbation readmission within 30 days but also an indirect factor through disease status; disease status and chronic disease are not only direct factors for acute exacerbation readmission within 30 days but also indirect factors through the patient's overall health status. CONCLUSIONS: The rate of patients with COPD presenting with acute exacerbation within 30 days is high; while taking measures to prevent readmission based on influencing factors that directly impact admission rates, attention should also be paid to the interaction between these factors.

Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-Omics Integrated Analysis.

OBJECTIVE: To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis. METHODS: Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO. RESULTS: A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process. CONCLUSIONS: CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.

Long non-coding RNAs as epigenetic mediator and predictor of glioma progression, invasiveness, and prognosis.

Gliomas are aggressive brain tumors with high mortality rate. Over the past several years, non-coding RNAs, specifically the long non-coding RNAs (lncRNAs), have emerged as biomarkers of considerable interest. Emerging data reveals distinct patterns of expressions of several lncRNAs in the glioma tissues, relative to their expression in normal brains. This has led to the speculation for putative exploitation of lncRNAs as diagnostic biomarkers as well as biomarkers for targeted therapy. With a focus on lncRNAs that have shown promise as epigenetic biomarkers in the proliferation, migration, invasion, angiogenesis and metastasis in various glioma models, we discuss several such lncRNAs. The data from cell line / animal model-based studies as well as analysis from human patient samples is presented for the most up-to-date information on the topic. Overall, the information provided herein makes a compelling case for further evaluation of lncRNAs in clinical settings.

Biallelic XPR1 mutation associated with primary familial brain calcification presenting as paroxysmal kinesigenic dyskinesia with infantile convulsions.

BACKGROUND: Mutations in the XPR1 gene are associated with primary familial brain calcifications (PFBC). All reported mutations are missense and inherited as an autosomal dominant trait. PFBC patients exhibited movement disorders, neuropsychiatric symptoms, and other associated symptoms with diverse severity, even within the same family. MATERIALS AND METHODS: We identified and enrolled a patient with PFBC. Clinical data were comprehensively collected, including the age of onset, seizure types and frequency, trigger factors of paroxysmal dyskinesia, response to drugs, and general and neurological examination results. Whole-exome sequencing (WES) was performed to detect pathogenic variants. We further systematically reviewed the phenotypic and genetic features of patients with XPR1 mutations. RESULTS: The patient showed bilateral calcification involving basal ganglia and cerebellar dentate. Clinically, he presented as paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) with favorable outcome. We identified a compound heterozygous XPR1 mutation (c.786_789delTAGA/p.D262Efs*6, c.1342C>T/p.R448W), which were inherited from unaffected parents respectively. Further literature review shows a wide range of clinical manifestations of patients with XPR1 mutations, with movement disorders being the most common. CONCLUSIONS: This is the first report of biallelic mutations in XPR1. The findings suggest for the first time a possible link between PKD/IC and XPR1 mutations.

WTAP Function in Sertoli Cells Is Essential for Sustaining the Spermatogonial Stem Cell Niche.

Sertoli cells are the major component of the spermatogonial stem cell (SSC) niche; however, regulatory mechanisms in Sertoli cells that dictate SSC fate decisions remain largely unknown. Here we revealed features of the N6-methyladenosine (m6A) mRNA modification in Sertoli cells and demonstrated the functions of WTAP, the key subunit of the m6A methyltransferase complex in spermatogenesis. m6A-sequencing analysis identified 21,909 m6A sites from 15,365 putative m6A-enriched transcripts within 6,122 genes, including many Sertoli cell-specific genes. Conditional deletion of Wtap in Sertoli cells resulted in sterility and the progressive loss of the SSC population. RNA sequencing and ribosome nascent-chain complex-bound mRNA sequencing analyses suggested that alternative splicing events of transcripts encoding SSC niche factors were sharply altered and translation of these transcripts were severely dysregulated by Wtap deletion. Collectively, this study uncovers a novel regulatory mechanism of the SSC niche and provide insights into molecular interactions between stem cells and their cognate niches in mammals.

Neuroprotective effect of resveratrol against radiation after surgically induced brain injury by reducing oxidative stress, inflammation, and apoptosis through NRf2/HO-1/NF-κB signaling pathway.

The impact of resveratrol (RSV) on radiation (RAD)-induced brain injury in rats' brains was investigated. A total of 40 male Wistar Albino rats were randomly divided into four groups (control, RAD, RAD + RSV, and RSV groups, with 10 rats in each group). The results revealed a significant decrease in catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities, as well as glutathione (GSH) content. Further, a significant elevation in malondialdehyde, nitric oxide, interleukin-1-beta (IL-1ß), IL-6, and transforming growth factor-ß1 levels were observed. Furthermore, decreased B-cell lymphoma 2 (Bcl-2), increased Bcl-2-associated X, and tumor necrosis factor-α genes expression, decreased nuclear factor erythroid-related factor 2, heme oxygenase-1, and increased nuclear factor-κB protein levels were noticed. Also, an apoptosis marker, caspase-3-positive cells, was seen in the hippocampus. Those effects were observed in the RAD group of rats. The treatment of RSV displayed a significant amendment of the studied parameters in the brain tissues of the RAD group of animals. This effect is interrelated to the ability of RSV to scavenge the free radicals, enhance the activity of the antioxidant enzymes, increase GSH contents, and downregulate the inflammatory responses and apoptosis markers in the brain tissues of RAD animals. In conclusion, this study demonstrated that the potent antioxidant, anti-inflammatory, and antiapoptotic activities of RSV can improve the antioxidant status and suppress the inflammatory responses and apoptosis in the brain tissues of RAD animals.

Angelica Dahurica ethanolic extract improves impaired wound healing by activating angiogenesis in diabetes.

Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE) in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation. The angiogenic property of ADEE was subsequently verified ex vivo using aortic ring assays. Furthermore, we investigated the in vitro angiogenic activity of ADEE and its underlying mechanisms using human umbilical vein endothelial cells. ADEE treatment induced HUVECs proliferation, migration, and tube formation, which are typical phenomena of angiogenesis, in dose-dependent manners. These effects were associated with activation of angiogenic signal modulators, including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, endothelial nitric oxide synthase (eNOS) as well as increased NO production, and independent of affecting VEGF expression. ADEE-induced angiogenic events were inhibited by the MEK inhibitor PD98059, the PI3K inhibitor Wortmannin, and the eNOS inhibitor L-NAME. Our findings highlight an angiogenic role of ADEE and its ability to protect against impaired wound healing, which may be developed as a promising therapy for impaired angiogenesis and delayed wound healing in diabetes.

[Transcriptome analysis of response to heavy metal Cd stress in soybean root]. / å¤§è±†æ ¹ç³»åº”ç­”é‡é‡‘å±žCd胁迫的转录组分析.

Cadmium (Cd) is a common pollutant not required for life activities, which can have extremely strong toxicity to organisms and affect the growth of crops at a low concentration in soil. To investigate the molecular mechanism of soybean root responding to Cd stress, 7-day old soybean seedlings were stressed by Cd (75 Μmol·L-1) for 0 , 4 , 8, 12 and 48 h. Comparative transcriptome analysis showed 244, 1545, 442 and 1401 of genes responded to the four Cd treatments, respectively, and total 2670 differential expression genes were obtained. GO analysis classified these genes into 56 functional categories and COG analysis classified them into 25 functional categories. KEGG analysis showed that many genes involved in the phenylalanine metabolism, ubiquinone and other terpenoid-quinone biosynthesis and cysteine and methionine metabolism and so on. Further we found that expression of three isoflavones 2'-hydroxylase genes, two isoflavonereductase genes and a chalcone synthase gene were evidently up-regulated in all Cd treatments. The results of RT-PCR analysis of four DEGs were consistent with those of RNA-Seq data, further confirming the reliability of RNA-Seq results.

The Four-Herb Chinese Medicine Formula Tuo-Li-Xiao-Du-San Accelerates Cutaneous Wound Healing in Streptozotocin-Induced Diabetic Rats through Reducing Inflammation and Increasing Angiogenesis.

Impaired wound healing in diabetic patients is a serious complication that often leads to amputation or even death with limited effective treatments. Tuo-Li-Xiao-Du-San (TLXDS), a traditional Chinese medicine formula for refractory wounds, has been prescribed for nearly 400 years in China and shows good efficacy in promoting healing. In this study, we explored the effect of TLXDS on healing of diabetic wounds and investigated underlying mechanisms. Four weeks after intravenous injection of streptozotocin, two full-thickness excisional wounds were created with a 10 mm diameter sterile biopsy punch on the back of rats. The ethanol extract of TLXDS was given once daily by oral gavage. Wound area, histological change, inflammation, angiogenesis, and collagen synthesis were evaluated. TLXDS treatment significantly accelerated healing of diabetic rats and improved the healing quality. These effects were associated with reduced neutrophil infiltration and macrophage accumulation, enhanced angiogenesis, and increased collagen deposition. This study shows that TLXDS improves diabetes-impaired wound healing.

Enhanced antitumor immunity is elicited by adenovirus-mediated gene transfer of CCL21 and IL-15 in murine colon carcinomas.

The chemokine CCL21 is a potent chemoattractant for T cells and dendritic cells. IL-15 elicits powerful antitumor immune responses through the stimulation of natural killer cells. We constructed a CCL21/IL-15-expressing adenovirus (Ad-CCL21-IL-15) and evaluated its antitumor effects in vitro and in vivo. We found that the intratumoral injection of Ad-CCL21-IL-15 into murine colon carcinomas significantly inhibited tumor growth. Splenocytes from mice treated with Ad-CCL21-IL-15 developed tumor-specific cytotoxic T cells and were protected from subsequent challenges with tumor cells. This study indicates that providing cancer therapy by combining CCL21 and IL-15 can induce antitumor immune responses and is an effective strategy for cancer immunotherapy.

The mechanism of mimecan transcription induced by glucocorticoid in pituitary corticotroph cells.

Mimecan, a secretary protein that is expressed in mouse and human pituitary corticotroph cells, is up-regulated by glucocorticoids (GC) in the corticotroph cells via classical glucocorticoid receptor (GR) pathways. In this study, we further explore the GC mechanism for mimecan expression in these cells. Five putative GR response elements (GREs) were identified in ~2 kb of the mimecan promoter by programme analysis. An EMSA assay further indicated that these putative GREs were bound by the GR. Moreover, three proximal GREs are conserved between species. Although luciferase assays showed that the -1474/+43 region of the mimecan promoter achieved the highest expression of mimecan, the -803/+43 mimecan promoter region was sufficient for the GC-mediated expression of mimecan. The mutations of three conserved GREs located in the -1474/+43 mimecan promoter region did not affect mimecan transcription, which suggests that the effects of GC on mimecan are independent of the GREs in the promoter. In addition, cycloheximide, a protein synthesis inhibitor, blocked GC-induced mimecan expression in AtT-20 cells. Taken together, these results suggest that, although there are 3-5 GREs in the mimecan promoter, GC may regulate mimecan transcription indirectly through the synthesis of intermediate proteins and not through the GREs in pituitary corticotroph cells.

Mimecan in pituitary corticotroph cells may regulate ACTH secretion and the HPAA.

Mimecan is a protein of unknown function that is expressed in the pituitary tissues of mouse and human. In this study, we observed the function of mimecan on the proopiomelanocortin (POMC) gene in the pituitary and the hypothalamo-pituitary-adrenal axis (HPAA). Incubating pituitary corticotroph AtT-20 cells with recombinant mimecan protein stimulated adrenocorticotrophic hormone (ACTH) secretion without significantly up-regulating POMC gene expression. In addition, pituitary corticotroph AtT-20 cell corticotropin-releasing hormone receptor 1 (CRHR1) gene expression was induced by mimecan. Interestingly, long-term mimecan overexpression in corticotroph cells increased CRHR1 mRNA levels while slightly decreasing POMC mRNA expression and ACTH secretion. Using mimecan knockout mice, we found that, although the serum ACTH concentration was not significantly different between wild type and mimecan knockout mice under basal conditions, the serum ACTH level was relatively lower in mimecan knockout mice after treatment with corticotropin-releasing hormone (CRH). Meanwhile, we observed that POMC and CRHR1 gene expression decreased in primary cultured knockout mouse pituitary cells compared with wild type cells. Taken together, these data suggest that mimecan expressed in pituitary corticotroph cells mainly regulates ACTH secretion in the pituitary and coordinates the HPAA.

Genome-wide analysis of microRNA and mRNA expression signatures in hydroxycamptothecin-resistant gastric cancer cells.

AIM: To investigate the involvement of microRNAs (miRNAs) in intrinsic drug resistance to hydroxycamptothecin (HCPT) of six gastric cancer cell lines (BGC-823, SGC-7901, MGC-803, HGC-27, NCI-N87, and AGS). METHODS: A sulforhodamine B (SRB) assay was used to analyze the sensitivity to HCPT of six gastric cancer cell lines. The miRNA and mRNA expression signatures in HCPT-resistant cell lines were then identified using DNA microarrays. Gene ontology and pathway analysis was conducted using GenMAPP2. A combined analysis was used to explore the relationship between the miRNAs and mRNAs. RESULTS: The sensitivity to HCPT was significantly different among the six cell lines. In the HCPT-resistant gastric cancer cells, the levels of 25 miRNAs were deregulated, including miR-196a, miR-200 family, miR-338, miR-126, miR-31, miR-98, let-7g, and miR-7. Their target genes were related to cancer development, progression and chemosensitivity. Moreover, 307 genes were differentially expressed in HCPT-resistant cell lines, including apoptosis-related genes (BAX, TIAL1), cell division-related genes (MCM2), cell adhesion- or migration-related genes (TIMP2, VSNL1) and checkpoint genes (RAD1). The combined analysis revealed 78 relation pairs between the miRNAs and mRNAs. CONCLUSION: Hierarchical clustering showed that the miRNA and mRNA signatures in our results were informative for discriminating cell lines with different sensitivities to HCPT. However, there was slightly lower correlation between the expression patterns of the miRNA and those of the predicted target transcripts.

Retrospective study of photodynamic therapy vs photodynamic therapy combined with chemotherapy and chemotherapy alone on advanced esophageal cancer.

OBJECTIVE: To compare the short-term curative effect of photodynamic therapy (PDT), PDT combined with chemotherapy and chemotherapy alone on the advanced esophageal cancer patients. METHODS: Retrospective analysis of 90 patients of esophageal cancer underwent PDT, PDT combined with chemotherapy and chemotherapy alone from 2004 to 2007 (stages III-IV), including 27 cases received PDT alone, 33 cases received PDT combined with chemotherapy and 30 cases chemotherapy alone. The enrolled patients were treated with intravenous administration of Photofrin as the photosensitizer at a dose of 2mg/kg. 630 nm laser irradiation was performed through optical fiber that passed through the biopsy channel of a flexible endoscope after 48 h. Two days later, the necrotic tissue was removed, and the primary sites and other newly identified lesions were subjected to a second irradiation and then the residual necrotic tissue was removed according to the patients' condition. Electronic endoscopy was performed to observe the effectiveness on tumor after 1 month. In PDT combined with chemotherapy group, chemotherapy regimen was 5-FU and DDP, administered 4 cycles after PDT and chemotherapy alone group only chemotherapy regimen 5-FU and DDP for four cycles. All the 90 patients were followed up for 2 years. RESULTS: Symptomatic palliation rate of the PDT alone group, the complex treatment group and chemotherapy alone group was 85.2%, 93.9% and 60.0%, respectively, and effective rate under endoscopy was 85.2%, 90.9% and 63.3%, respectively, there is no statistically significant difference; the survival rate of 2 years was 29.6%, 54.5% and 16.7%, respectively, and medium survival time is longer (III stages 13 m, 22 m, 10 m; IV stages 7 m, 5m, 4m), there is statistically significant difference (p=0.046). CONCLUSION: PDT combined with chemotherapy for the advanced esophageal cancer is superior to PDT alone and chemotherapy alone.

Glucocorticoid up-regulates mimecan expression in corticotroph cells.

Mimecan is a protein of unknown function that is expressed in the pituitary. The aim of this study is to clarify the regulation and intracellular localisation of mimecan gene expression in the pituitary. With immunohistochemistry, we observed that mimecan protein was co-expressed with ACTH in pituitary corticotroph cells. Northern and Western blot analyses revealed that mimecan expression and secretion in corticotroph cells were up-regulated by treating AtT-20 cells with glucocorticoid. Meanwhile, mimecan expression in rat primary culture pituitary cells was also promoted by glucocorticoid. Co-incubation of AtT-20 cells with RU486 and glucocorticoid completely reversed the induction of mimecan gene expression by glucocorticoid. In addition, luciferase reporter assays showed that the -1474/+43 promoter region of mimecan was sufficient for glucocorticoid-responsive mimecan expression. These data collectively suggest that mimecan expressed in pituitary corticotroph cells is increased by glucocorticoid and that the up-regulation may be mediated by the classical GR pathways.

[Coronary computed tomographic angiography using low-dose prospectively electrocardiographic triggered high-pitch spiral acquisition by dual-source computed tomography: image quality and radiation dose].

OBJECTIVE: To evaluate image quality (IQ) and radiation exposure of coronary computed tomographic angiography (CTA) with prospectively electrocardiographic (ECG) triggered high-pitch spiral acquisition using dual source CT. METHODS: Totally 75 consecutive patients with a stable heart rate (HR) ≤65 bpm underwent coronary CTA. patients were divided into two groups according to their HR (group A HR≤60 bpm, group B HR >60 bpm to≤65 bpm) . A dual-source CT scanner was used (0.6mm collimation, 0.28s rotation time, 80~100 kV, 370 mAs/rot) . Data acquisition was prospectively ECG-triggered at 60% of the R-R interval with a pitch of 3.4. Images were reconstructed with 75ms temporal resolution, 0.75mm slice thickness and 0.5mm increment. IQ was evaluated using a four-point scale (1=excellent, 4=unevaluable) . RESULTS: The mean HR and scan time of all patients was (57.2 ± 4.8) bpm and (0.42 ± 0.02) s. Of 1103 coronary artery segments, 934 (84.7%) had an IQ score of 1, 135 (12.2%) score of 2, 18 (1.6%) score of 3,and 16 (1.5%) were rated as unevaluable. There was no significant difference between the two groups in IQ [mean score (1.19 ± 0.52 vs. 1.22 ± 0.55;Z=-1.107,P=0.268) . The rate of evaluable segments showed no significant difference between the two groups (98.5% vs. 98.6%;X2=0.000,P=1.000) . Mean dose-length product of all patients was (67.2 ± 30.4) mGy × cm, mean effective dose was (0.94 ± 0.43) mSv. CONCLUSION: In patients with a stable HR of 65 bpm or less, prospectively ECG-triggered high-pitch spiral CT acquisition provides high IQ at low radiation dose.

Expression of adiponectin receptors in mouse adrenal glands and the adrenocortical Y-1 cell line: adiponectin regulates steroidogenesis.

Obesity is frequently associated with malfunctions of the hypothalamus-pituitary-adrenal (HPA) axis and hyperaldosteronism, but the mechanism underlying this association remains unclear. Since the adrenal glands are embedded in adipose tissue, direct cross-talk between adipose tissue and the adrenal gland has been proposed. A previous study found that adiponectin receptor mRNA was expressed in human adrenal glands and aldosterone-producing adenoma (APA). However, the expression of adiponectin receptors in adrenal glands has not been confirmed at the protein level or in other species. Furthermore, it is unclear whether adiponectin receptors expressed in adrenal cells are functional. We found, for the first time, that adiponectin receptor (AdipoR1 and AdipoR2) mRNA and protein were expressed in mouse adrenal and adrenocortical Y-1 cells. However, adiponectin itself was not expressed in mouse adrenal or Y-1 cells. Furthermore, adiponectin acutely reduced basal levels of corticosterone and aldosterone secretion. ACTH-induced steroid secretion was also inhibited by adiponectin, and this was accompanied by a parallel change in the expression of the key genes involved in steroidogenesis. These findings indicate that adiponectin may take part in the modulation of steroidogenesis. Thus, adiponectin is likely to have physiological and/or pathophysiological significance as an endocrine regulator of adrenocortical function.

Spectrum of functioning islet cell tumor on multislice computed tomography: experience on 70 patients.

OBJECTIVE: To review experience in preoperative detection of islet cell tumors using multislice computed tomography (MSCT) and summarize various imaging features of functioning islet cell tumors on enhanced MSCT. METHODS: Seventy patients with clinical or pathological diagnosis of functioning pancreatic islet cell tumor between October 2003 and February 2007 were included in this retrospective study. Seventy-four enhanced MSCT scans in these patients were identified. All MSCT scans were interpreted by two experienced radiologists by consensus interpretation. Surgery and pathology reports were used to confirm the diagnosis, localization, and size of tumors. RESULTS: Totally, 73 functioning islet cell tumors including 65 benign insulinomas, 2 benign glucagonomas, 3 malignant insulinomas, and 3 malignant glucagonomas were pathologically diagnosed. Tumors in only two cases were not found by MSCT. In 67 benign lesions, 32 showed typical enhancement style, 21 showed prolonged enhancement in portal venous phase, 4 showed delayed enhancement, 4 had iso-dense enhancement with normal pancreatic parenchyma, 2 had no enhancement at all in arterial phase and portal venous phase, and 4 had inhomogeneous enhancement with necrosis or cyst-formation. Patchy or spotty calcifications were found in 3 of the 67 tumors. In 6 malignant islet cell tumors, vessel invasion (2/6) and bowel invasion (1/6) were seen. Different enhancement patterns were shown. All hepatic metastases showed hyper-enhancement during their arterial phase. CONCLUSIONS: Pancreatic islet cell tumor may display a wide spectrum of presentations in MSCT. Tumors with unusual appearances often present as diagnostic challenges. Non-contrast and post-contrast multiphase scans are recommended for the localization of functioning islet cell tumors.