Migration of the os peroneum: An enigmatic phenomenon explored through radiological perspectives.

The os peroneum is an accessory ossicle located along the lateral aspect of the cuboid bone. Its position can serve as an indicator of peroneus longus tendon (PLT) injury. Imaging studies including radiographs and MRI can help detect malposition of the os peroneum and progressive injuries to the PLT and its associated structures. We report a case of a woman with recurrent foot and ankle pain, demonstrating progressive retraction of the os peroneum, implying severe PLT injury which may have ultimately predisposed her to a traumatic fifth metatarsal base fracture. This case highlights the importance of scrutinizing the appearance and position of the os peroneum on radiographs.

Brain nuclei and neural circuits in neuropathic pain and brain modulation mechanisms of acupuncture: a review on animal-based experimental research.

Neuropathic pain (NP) is known to be associated with abnormal changes in specific brain regions, but the complex neural network behind it is vast and complex and lacks a systematic summary. With the help of various animal models of NP, a literature search on NP brain regions and circuits revealed that the related brain nuclei included the periaqueductal gray (PAG), lateral habenula (LHb), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC); the related brain circuits included the PAG-LHb and mPFC-ACC. Moreover, acupuncture and injurious information can affect different brain regions and influence brain functions via multiple aspects to play an analgesic role and improve synaptic plasticity by regulating the morphology and structure of brain synapses and the expression of synapse-related proteins; maintain the balance of excitatory and inhibitory neurons by regulating the secretion of glutamate, γ-aminobutyric acid, 5-hydroxytryptamine, and other neurotransmitters and receptors in the brain tissues; inhibit the overactivation of glial cells and reduce the release of pro-inflammatory mediators such as interleukins to reduce neuroinflammation in brain regions; maintain homeostasis of glucose metabolism and regulate the metabolic connections in the brain; and play a role in analgesia through the mediation of signaling pathways and signal transduction molecules. These factors help to deepen the understanding of NP brain circuits and the brain mechanisms of acupuncture analgesia.

A multi-subgroup predictive model based on clinical parameters and laboratory biomarkers to predict in-hospital outcomes of plasma exchange-centered artificial liver treatment in patients with hepatitis B virus-related acute-on-chronic liver failure.

Background: Postoperative risk stratification is challenging in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who undergo artificial liver treatment. This study characterizes patients' clinical parameters and laboratory biomarkers with different in-hospital outcomes. The purpose was to establish a multi-subgroup combined predictive model and analyze its predictive capability. Methods: We enrolled HBV-ACLF patients who received plasma exchange (PE)-centered artificial liver support system (ALSS) therapy from May 6, 2017, to April 6, 2022. There were 110 patients who died (the death group) and 110 propensity score-matched patients who achieved satisfactory outcomes (the survivor group). We compared baseline, before ALSS, after ALSS, and change ratios of laboratory biomarkers. Outcome prediction models were established by generalized estimating equations (GEE). The discrimination was assessed using receiver operating characteristic analyses. Calibration plots compared the mean predicted probability and the mean observed outcome. Results: We built a multi-subgroup predictive model (at admission; before ALSS; after ALSS; change ratio) to predict in-hospital outcomes of HBV-ACLF patients who received PE-centered ALSS. There were 110 patients with 363 ALSS sessions who survived and 110 who did not, and 363 ALSS sessions were analyzed. The univariate GEE models revealed that several parameters were independent risk factors. Clinical parameters and laboratory biomarkers were entered into the multivariate GEE model. The discriminative power of the multivariate GEE models was excellent, and calibration showed better agreement between the predicted and observed probabilities than the univariate models. Conclusions: The multi-subgroup combined predictive model generated accurate prognostic information for patients undergoing HBV-ACLF patients who received PE-centered ALSS.

Rutin promotes white adipose tissue "browning" and brown adipose tissue activation partially through the calmodulin-dependent protein kinase kinase ß/AMP-activated protein kinase pathway.

Promoting white adipose tissue (WAT) "browning" and brown adipose tissue (BAT) activation could contribute to increasing energy expenditure. We explored the mechanisms by which the natural compound rutin induced adipose tissue differentiation and ameliorated obesity in vivo and in vitro. 3T3-L1 preadipocytes were cultured in adipogenic differentiation media with/out rutin. Male C57BL/6 mice (n = 6) were fed a high-fat diet (HFD) for 12 weeks with/out rutin. In HFD-fed mice, rutin treatment significantly inhibited weight gain, improved the metabolic profile of plasma samples, decreased the weights of epididymal WAT (eWAT), inguina WAT (iWAT), and liver, and adipocyte size. Furthermore, rutin also increased the expression of uncoupling protein 1 (Ucp-1) and other thermogenic markers in the WAT and BAT. In 3T3-L1 cells, rutin effectively reduced the formation of lipid droplets, stimulated the expression of thermogenic markers, and reduced the expression of adipogenic genes. Additionally, rutin markedly upregulated the AMP-activated protein kinase (AMPK) pathway, and these effects were diminished by treatment with the AMPK inhibitor compound C (CC). Pretreatment with the calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor STO-609 blocked the induction of thermogenic markers in 3T3-L1 cells by rutin. Our results indicated that rutin increased energy consumption, induced WAT "browning" and BAT activation, and thus was a promising target for the development of new therapeutic approaches to improve adipose tissue energy metabolism.

Construction of a fungal consortium for effective degradation of rice straw lignin and potential application in bio-pulping.

To improve the lignin degradation efficiency, we established a co-culture consortium (LDFC) consisting of Trametes hirsuta BYL-3, Trametes versicolor BYL-7 and Trametes hirsuta BYL-8. The testing results showed that the constructed consortium showed improved the lignin degradation rate by fungi. The optimal cultivation conditions were mixture at 1:1:1 vol ratio of each fungus, 7% (w/v) of inoculum amount, culture temperature at 26 °C, pH was 6.9 and 10 days of culturing time. Under these conditions, the degradation rate of lignin was 39.7%, which was 9.3% higher than those before optimization (30.4%). Using rice straw for treatment by LDFC to papermaking, the paper tensile strength was 8 N, and the ring pressure index was 2.46 N·m/g, which meets the standards for the production of corrugated paper for packaging. These results indicate that LDFC has potential application value to convert rice straw resources for bio-pulping to make papers.

Metabolomics Identifies Biomarker Signatures to Differentiate Pancreatic Cancer from Type 2 Diabetes Mellitus in Early Diagnosis.

METHODS: Plasma metabolic profiles in 26 PC patients, 27 DM patients, and 23 healthy volunteers were examined using an ultraperformance liquid chromatography coupled with tandem mass spectrometry platform. Differential metabolite ions were then identified using the principal component analysis (PCA) model and the orthogonal partial least-squares discrimination analysis (OPLS-DA) model. The diagnosis performance of metabolite biomarkers was validated by logistic regression models. RESULTS: We established a PCA model (R2X = 23.5%, Q2 = 8.21%) and an OPLS-DA model (R2X = 70.0%, R2Y = 84.9%, Q2 = 69.7%). LysoPC (16 : 0), catelaidic acid, cerebronic acid, nonadecanetriol, and asparaginyl-histidine were found to identify PC, with a sensitivity of 89% and a specificity of 91%. Besides, lysoPC (16 : 0), lysoPC (16 : 1), lysoPC (22 : 6), and lysoPC (20 : 3) were found to differentiate PC from DM, with higher accuracy (68% versus 55%) and higher AUC values (72% versus 63%) than those of CA19-9. The diagnostic performance of metabolite biomarkers was finally validated by logistic regression models. CONCLUSION: We succeeded in screening differential metabolite ions among PC and DM patients and healthy individuals, thus providing a preliminary basis for screening the biomarkers for the early diagnosis of PC.

Clinical Parameters and Metabolomic Biomarkers That Predict Inhospital Outcomes in Patients With ST-Segment Elevated Myocardial Infarctions.

BACKGROUND: Postoperative risk stratification is challenging in patients with ST-segment elevation myocardial infarction (STEMI) who undergo percutaneous coronary intervention. This study aimed to characterize the metabolic fingerprints of patients with STEMI with different inhospital outcomes in the early stage of morbidity and to integrate the clinical baseline characteristics to develop a prognostic prediction model. METHODS: Plasma samples were collected retrospectively from two propensity score-matched STEMI cohorts from May 6, 2020 to April 20, 2021. Cohort 1 consisted of 48 survivors and 48 non-survivors. Cohort 2 included 48 patients with unstable angina pectoris, 48 patients with STEMI, and 48 age- and sex-matched healthy controls. Metabolic profiling was generated based on ultra-performance liquid chromatography and a mass spectrometry platform. The comprehensive metabolomic data analysis was performed using MetaboAnalyst version 5.0. The hub metabolite biomarkers integrated into the model were tested using multivariate linear support vector machine (SVM) algorithms and a generalized estimating equation (GEE) model. Their predictive capabilities were evaluated using areas under the curve (AUCs) of receiver operating characteristic curves. RESULTS: Metabonomic analysis from the two cohorts showed that patients with STEMI with different outcomes had significantly different clusters. Seven differentially expressed metabolites were identified as potential candidates for predicting inhospital outcomes based on the two cohorts, and their joint discriminative capabilities were robust using SVM (AUC = 0.998, 95% CI 0.983-1) and the univariate GEE model (AUC = 0.981, 95% CI 0.969-0.994). After integrating another six clinical variants, the predictive performance of the updated model improved further (AUC = 0.99, 95% CI 0.981-0.998). CONCLUSION: A survival prediction model integrating seven metabolites from non-targeted metabonomics and six clinical indicators may generate a powerful early survival prediction model for patients with STEMI. The validation of internal and external cohorts is required.

Radiomic Features of the Nigrosome-1 Region of the Substantia Nigra: Using Quantitative Susceptibility Mapping to Assist the Diagnosis of Idiopathic Parkinson's Disease.

Introduction: The loss of nigrosome-1, which is also referred to as the swallow tail sign (STS) in T2*-weighted iron-sensitive magnetic resonance imaging (MRI), has recently emerged as a new biomarker for idiopathic Parkinson's disease (IPD). However, consistent recognition of the STS is difficult due to individual variations and different imaging parameters. Radiomics might have the potential to overcome these shortcomings. Therefore, we chose to explore whether radiomic features of nigrosome-1 of substantia nigra (SN) based on quantitative susceptibility mapping (QSM) could help to differentiate IPD patients from healthy controls (HCs). Methods: Three-dimensional multi-echo gradient-recalled echo images (0.86 × 0.86 × 1.00 mm3) were obtained at 3.0-T MRI for QSM in 87 IPD patients and 77 HCs. Regions of interest (ROIs) of the SN below the red nucleus were manually drawn on both sides, and subsequently, volumes of interest (VOIs) were segmented (these ROIs included four 1-mm slices). Then, 105 radiomic features (including 18 first-order features, 13 shape features, and 74 texture features) of bilateral VOIs in the two groups were extracted. Forty features were selected according to the ensemble feature selection method, which combined analysis of variance, random forest, and recursive feature elimination. The selected features were further utilized to distinguish IPD patients from HC using the SVM classifier with 10 rounds of 3-fold cross-validation. Finally, the representative features were analyzed using an unpaired t-test with Bonferroni correction and correlated with the UPDRS-III scores. Results: The classification results from SVM were as follows: area under curve (AUC): 0.96 ± 0.02; accuracy: 0.88 ± 0.03; sensitivity: 0.89 ± 0.06; and specificity: 0.87 ± 0.07. Five representative features were selected to show their detailed difference between IPD patients and HCs: 10th percentile and median in IPD patients were higher than those in HCs (all p < 0.00125), while Gray Level Run Length Matrix (GLRLM)-Long Run Low Gray Level Emphasis, Gray Level Size Zone Matrix (GLSZM)-Gray Level Non-Uniformity, and volume (all p < 0.00125) in IPD patients were lower than those in HCs. The 10th percentile was positively correlated with UPDRS-III score (r = 0.35, p = 0.001). Conclusion: Radiomic features of the nigrosome-1 region of SN based on QSM could be useful in the diagnosis of IPD and could serve as a surrogate marker for the STS.

Computerized cognitive training for Chinese mild cognitive impairment patients: A neuropsychological and fMRI study.

BACKGROUND: Computerized multi-model training has been widely studied for its effect on delaying cognitive decline. In this study, we designed the first Chinese-version computer-based multi-model cognitive training for mild cognitive impairment (MCI) patients. Neuropsychological effects and neural activity changes assessed by functional MRI were both evaluated. METHOD: MCI patients in the training group were asked to take training 3-4 times per week for 6 months. Neuropsychological and resting-state fMRI assessment were performed at baseline and at 6 months. Patients in both groups were continuously followed up for another 12 months and assessed by neuropsychological tests again. RESULTS: 78 patients in the training group and 63 patients in the control group accomplished 6-month follow-up. Training group improved 0.23 standard deviation (SD) of mini-mental state examination, while control group had 0.5 SD decline. Addenbrooke's cognitive examination-revised scores in attention (p = 0.002) and memory (p = 0.006), as well as stroop color-word test interference index (p = 0.038) and complex figure test-copy score (p = 0.035) were also in favor of the training effect. Difference between the changes of two groups after training was not statistically significant. The fMRI showed increased regional activity at bilateral temporal poles, insular cortices and hippocampus. However, difference between the changes of two groups after another 12 months was not statistically significant. CONCLUSIONS: Multi-model cognitive training help MCI patients to gained cognition benefit, especially in memory, attention and executive function. Functional neuroimaging provided consistent neural activation evidence. Nevertheless, after one-year follow up after last training, training effects were not significant. The study provided new evidence of beneficial effect of multi-model cognitive training.

Abnormal Voxel-Wise Degree Centrality in Patients With Late-Life Depression: A Resting-State Functional Magnetic Resonance Imaging Study.

OBJECTIVES: Late-life depression (LLD) has negative impacts on somatic, emotional and cognitive domains of the lives of patients. Elucidating the abnormality in the brain networks of LLD patients could help to strengthen the understanding of LLD pathophysiology, however, the studies exploring the spontaneous brain activity in LLD during the resting state remain limited. This study aimed at identifying the voxel-level whole-brain functional connectivity changes in LLD patients. METHODS: Fifty patients with late-life depression (LLD) and 33 healthy controls were recruited. All participants underwent a resting-state functional magnetic resonance imaging scan to assess the voxel-wise degree centrality (DC) changes in the patients. Furthermore, DC was compared between two patient subgroups, the late-onset depression (LOD) and the early-onset depression (EOD). RESULTS: Compared with the healthy controls, LLD patients showed increased DC in the inferior parietal lobule, parahippocampal gyrus, brainstem and cerebellum (p < 0.05, AlphaSim-corrected). LLD patients also showed decreased DC in the somatosensory and motor cortices and cerebellum (p < 0.05, AlphaSim-corrected). Compared with EOD patients, LOD patients showed increased centrality in the superior and middle temporal gyrus and decreased centrality in the occipital region (p < 0.05, AlphaSim-corrected). No significant correlation was found between the DC value and the symptom severity or disease duration in the patients after the correction for multiple comparisons. CONCLUSIONS: These findings indicate that the intrinsic abnormality of network centrality exists in a wide range of brain areas in LLD patients. LOD patients differ with EOD patients in cortical network centrality. Our study might help to strengthen the understanding of the pathophysiology of LLD and the potential neural substrates underlie related emotional and cognitive impairments observed in the patients.

Improved Neuroimaging Atlas of the Dentate Nucleus.

The dentate nucleus (DN) of the cerebellum is the major output nucleus of the cerebellum and is rich in iron. Quantitative susceptibility mapping (QSM) provides better iron-sensitive MRI contrast to delineate the boundary of the DN than either T2-weighted images or susceptibility-weighted images. Prior DN atlases used T2-weighted or susceptibility-weighted images to create DN atlases. Here, we employ QSM images to develop an improved dentate nucleus atlas for use in imaging studies. The DN was segmented in QSM images from 38 healthy volunteers. The resulting DN masks were transformed to a common space and averaged to generate the DN atlas. The center of mass of the left and right sides of the QSM-based DN atlas in the Montreal Neurological Institute space was -13.8, -55.8, and -36.4 mm, and 13.8, -55.7, and -36.4 mm, respectively. The maximal probability and mean probability of the DN atlas with the individually segmented DNs in this cohort were 100 and 39.3%, respectively, in contrast to the maximum probability of approximately 75% and the mean probability of 23.4 to 33.7% with earlier DN atlases. Using QSM, which provides superior iron-sensitive MRI contrast for delineating iron-rich structures, an improved atlas for the dentate nucleus has been generated. The atlas can be applied to investigate the role of the DN in both normal cortico-cerebellar physiology and the variety of disease states in which it is implicated.

Dentate nucleus iron deposition is a potential biomarker for tremor-dominant Parkinson's disease.

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0-T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug-naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright © 2016 John Wiley & Sons, Ltd.

Serum Metabonomics of Mild Acute Pancreatitis.

BACKGROUND: Mild acute pancreatitis (MAP) is a common acute abdominal disease, and exhibits rising incidence in recent decades. As an important component of systemic biology, metabonomics is a new discipline developed following genomics and proteomics. In this study, the objective was to analyze the serum metabonomics of patients with MAP, aiming to screen metabolic markers with potential diagnostic values. METHODS: An analysis platform with ultra performance liquid chromatography-high-resolution mass spectrometry was used to screen the difference metabolites related to MAP diagnosis and disease course monitoring. RESULTS: A total of 432 endogenous metabolites were screened out from 122 serum samples, and 49 difference metabolites were verified, among which 12 difference metabolites were identified by nonparametric test. After material identification, eight metabolites exhibited reliable results, and their levels in MAP serum were higher than those in healthy serum. Four metabolites exhibited gradual downward trend with treatment process going on, and the differences were statistically significant (P < 0.05). CONCLUSION: Metabonomic analysis has revealed eight metabolites with potential diagnostic values toward MAP, among which four metabolites can be used to monitor the disease course.

Development of integrins in the vasculature of germinal matrix, cerebral cortex, and white matter of fetuses and premature infants.

Germinal matrix (GM) vasculature is selectively vulnerable to hemorrhage in premature infants during the first 48 hr of life. This is attributed to rapid angiogenesis of this brain region, resulting in formation of nascent vessels that show a paucity of pericytes and immaturity of extracellular matrix. Integrins are key regulators of angiogenesis and contribute to stabilization of cerebral vasculature by providing endothelial- and astrocyte-matrix adhesion. Therefore, we asked whether GM exhibited a distinct regional pattern of integrin expression that was dissimilar from that of the cerebral cortex and white matter in human fetuses and premature infants. To this end, we measured protein and gene expression of integrins in the GM, cortex, and white matter of human fetuses (15-22 weeks), premature infants (23-35 weeks), and mature infants (36-40 weeks). We found that protein levels of alpha5beta1 integrin were greater in the GM than in the cortex or white matter by 1.6-fold for both fetuses and premature infants. alpha5beta1 integrin mRNA expression was higher in the GM than in the cortex or white matter by 2-fold for fetuses but not for premature infants. alphaVbeta3, alphaVbeta5, alphaVbeta8, and alpha4beta1 integrin expression were comparable among GM, cortex, and white matter in fetuses and premature infants. Because alpha5beta1 integrin is a central regulator of angiogenesis, its elevation in the GM of fetuses and premature infants indicates that this might be a key activator of endothelial proliferation in this brain region. We speculate that selective alpha5beta1 integrin inhibition might suppress angiogenesis in the GM and thus prevent brain hemorrhage in premature infants.

Characterization of acute brain injuries and neurobehavioral profiles in a rabbit model of germinal matrix hemorrhage.

BACKGROUND AND PURPOSE: Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is the most common neurological problem of premature infants and has enormous financial and social impact. Despite this, there is no standardized animal model of IVH depicting acute brain injuries. METHODS: We delivered rabbit-pups prematurely at 29-day gestation by C-section, administered intraperitoneal glycerol to the pups at 3-hour postnatal age to induce IVH, and evaluated the brain for evidence of injuries. RESULTS: About 80% of glycerol-treated pups developed gross IVH. We found greater neutrophil and microglia infiltration around the ventricles (periventricular zone) in pups with IVH than in controls. We noted more apoptosis and neuronal degeneration in the periventricular zone than in the neocortex in pups with IVH, but not in controls. There was evidence of axonal damage revealed by beta-amyloid precursor protein and neurofilament immunolabeling. Neurobehavioral testing showed that pups with IVH were more wobbly with lesser capability to walk on inclination than pups without IVH. There was no evidence of acute systemic toxicity in the glycerol-treated pups. An evaluation of autopsy materials from premature infants revealed similar evidence of apoptosis and cellular infiltration in the periventricular zone in cases with IVH, but not in cases without IVH-suggesting clinical relevance of the model. CONCLUSIONS: The study provides an instructive animal model of IVH with evidence of acute brain injuries that can be used to evaluate strategies in prevention of IVH and acute posthemorrhagic complications.

Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone.

Germinal matrix is selectively vulnerable to hemorrhage in premature infants, and use of prenatal betamethasone is associated with a lower occurrence of germinal matrix hemorrhage. Because the major components of extracellular matrix of the cerebral vasculature-laminin, fibronectin, collagen IV, and perlecan-provide structural stability to blood vessels, we examined whether the expression of these molecules was decreased in the germinal matrix and affected by betamethasone. In both human fetuses and premature infants, fibronectin was significantly lower in the germinal matrix than in the cortical mantle or white matter anlagen. Conversely, laminin alpha1 gene expression was greater in the human germinal matrix compared with the cortical mantle or white matter. Expression of alpha1- and alpha2(IV) collagen chains increased with advancing gestational age. Low-dose prenatal betamethasone treatment enhanced fibronectin level by 1.5-2-fold whereas a high dose reduced fibronectin expression by 2-fold in rabbit pups. Because fibronectin provides structural stability to the blood vessels, its reduced expression in the germinal matrix may contribute to the fragility of germinal matrix vasculature and the propensity to hemorrhage in premature neonates.

Paucity of pericytes in germinal matrix vasculature of premature infants.

Germinal matrix (GM) is a richly vascularized collection of neuronal-glial precursor cells in the developing brain, which is selectively vulnerable to hemorrhage in premature infants. It has rapid angiogenesis associated with high levels of vascular endothelial growth factor (VEGF). Because pericytes provide structural stability to blood vessels, we asked whether pericytes were fewer in the GM than in the subjacent white matter and neocortex and, if so, whether angiogenic inhibition could increase the pericyte density in the GM. We found pericyte coverage and density less in the GM vasculature than in the cortex or white matter in human fetuses, premature infants, and premature rabbit pups. Notably, although VEGF suppression significantly enhanced pericyte coverage in the GM, it remained less than in other brain regions. Therefore, to further elucidate the basis of fewer pericytes in the GM vasculature, we examined expression of ligand-receptor systems responsible for pericyte recruitment. Transforming growth factor-beta1 (TGF-beta1) protein expression was lower, whereas sphingosine-1-phosphate1 (S1P1) and N-cadherin levels were higher in the GM than in the cortex or white matter. Low TGF-beta1 may be involved in promoting endothelial proliferation, whereas elevated S1P1 with N-cadherin may assist vascular maturation. Hence, a paucity of pericytes in the GM vasculature may contribute to its propensity to hemorrhage, and a lower expression of TGF-beta1 could be a basis of reduced pericyte density in its vasculature.

Angiogenic inhibition reduces germinal matrix hemorrhage.

The germinal matrix of premature infants is selectively vulnerable to hemorrhage within the first 48 h of life. To assess the role of vascular immaturity in germinal matrix hemorrhage (GMH), we evaluated germinal matrix angiogenesis in human fetuses and premature infants, as well as in premature rabbit pups, and noted active vessel remodeling in all three. Vascular endothelial growth factor (VEGF), angiopoietin-2 and endothelial cell proliferation were present at consistently higher levels in the germinal matrix relative to the white matter anlagen and cortical mantle. On that basis, we asked whether prenatal treatment with either of two angiogenic inhibitors, the COX-2 inhibitor celecoxib, or the VEGFR2 inhibitor ZD6474, could suppress the incidence of GMH in premature rabbit pups. Celecoxib treatment decreased angiopoietin-2 and VEGF levels as well as germinal matrix endothelial proliferation. Furthermore, treatment with celecoxib or ZD6474 substantially decreased the incidence of GMH. Thus, by suppressing germinal matrix angiogenesis, prenatal celecoxib or ZD6474 treatment may be able to reduce both the incidence and severity of GMH in susceptible premature infants.

[Screening of differentially expressed genes in colorectal cancer using human whole genomic oligonucleotide microarrays].

OBJECTIVE: To screen the differentially expressed genes in human colorectal cancer (CRC) tissue. METHODS: Affymetrix oligonucleotide microarrays HG-U133 representing 32,264 human genes including 19,308 known genes and 12,956 expressed sequence tags (ESTs) were used to detect the gene expressions of CRC tissue paired with normal mucosa tissue. The microarray findings were confirmed by real-time quantitative reverse transcriptase-polymerase chain reaction (FQ-PCR). The gene expression profiles were analyzed by intersection and complement, rank sum test and t test. RESULTS: Totally 3,125 genes and ESTs expressed differentially were detected in normal and cancer tissues, consisting of 974 up-regulated and 2,151 down-regulated genes with 247 ESTs present in CRC tissue and absent in normal mucosa and 162 ESTs absent in CRC tissue but present in normal mucosa. A percent of 80.1% of the differentially expressed genes were not reported in the literatures. CONCLUSION: The strategy of data mining provides a foundation for filtering molecular markers and interpreting molecular carcinogenesis of CRC.