Clinical significance of intracavitary electrocardiographic localization in the prevention of PICC heterotopia in children with tumor.

OBJECTIVE: To explore the clinical significance of intracavitary electrocardiogram positioning technology in preventing catheter ectopic position during peripherally inserted central catheter (PICC) catheterization in children with tumors. METHODS: A retrospective analysis of the clinical data of 62 children who required PICC catheterization was performed. The intracavitary electrocardiogram (ECG) positioning technology was used during the tube placement of the child patients. After the tube was successfully placed, the chest radiograph was taken. The ECG positioning result was compared with the chest radiograph positioning result after the tube was inserted, and the sensitivity and specificity of the ECG positioning were calculated. RESULTS: The intracavitary electrocardiogram results of 62 children with PICC catheters showed that 56 cases (90.32%) had characteristic P waves, and six cases (9.68%) had no characteristic P waves. The chest radiographs of 56 children with characteristic P wave showed that 33 cases (58.93%) of the catheter tip position was appropriate, 22 cases (39.29%) of the catheter tip was too deep, and 1 case was in a non-superior vena cava; six cases of chest radiographs of children with no characteristic P wave showed: one case was too deep at T8 level, one case was too shallow at T4 level, four cases were at non-superior vena cava, one case was contralateral internal jugular vein, two cases in the contralateral brachiocephalic vein, and one case was the contralateral subclavian vein. CONCLUSION: Intracavitary ECG positioning assisted catheter placement in infants can effectively improve the accuracy of catheter tip position.

ECG method for positioning the tip of peripherally inserted central catheters in patients with atrial fibrillation.

OBJECTIVE: To observe the changes of F waves on electrocardiograms (ECGs) in patients with persistent atrial fibrillation during the insertion of a peripherally inserted central catheter (PICC), and to analyze the application effect of the ECG method (through F wave changes) for guiding PICC tip positioning. METHODS: Seventy-two patients who met the inclusion criteria and needed a PICC catheter were selected as the research subjects. We observed waveforms in the ECGs when the tip of the catheter reached a predetermined position. The chest X-ray results were used as the gold standard to calculate the sensitivity and specificity, and judge the safety and accuracy of ECG-guided PICC tip positioning in patients with atrial fibrillation. RESULTS: Of the 72 patients, there was no significant difference between the ECG method and chest X-ray results (χ2 = 0.2, p > 0.05). Sixty-one patients had F wave changes on ECG and 10 had no obvious changes (X-ray results confirmed that five patients had a tip position that was too shallow, two had ectopic tip positions, and three were located in the correct place). The sensitivity of the method was 95.7% and the specificity was 80%. CONCLUSION: As the ECG baselines of patients with persistent atrial fibrillation were difficult to judge and the F wave was irregular, we found that the F wave was significantly higher than before catheter insertion and fell back while withdrawing the catheter, so the catheter should be fed until the F wave significantly increased as the correct position of the catheter tip.

Serum leptin level measured 48 h after delivery is associated with development of postpartum depressive symptoms: a 3-month follow-up study.

The aim of this study was to assess the possible relationship between leptin status and postpartum depressive symptoms using serum levels of leptin collected 24-48 h after delivery in a cohort Chinese sample. Women delivering a full-term, singleton, and live-born infant in the period from August 2013 to March 2014 were enrolled immediately postpartum. A blood sample was obtained 24-48 h after childbirth to test serum levels of leptin. Participation consisted of a visit in an obstetric unit at 3 months after delivery. The Edinburgh Postnatal Depression Scale (EPDS), completed at 3 months postpartum, was used to classify each woman's depression symptom severity. Demographic, obstetric, behavioral risk, mental health, and psychosocial factors were considered. Multiple logistic regression analyses were used to identify risk factors most predictive of postpartum depressive symptoms. During the study period, 407 individuals were included and completed follow-up. At 3 months, according to EPDS score, 53 women (13.0 %) were considered as postpartum depressive symptoms. Serum leptin levels in women with PPD were significantly greater than those in women without depressive symptoms (36.5 [IQR, 25.5-50.4] vs. 14.5 [IQR, 9.4-22.4] ng/ml, P < 0.0001). Based on the ROC curve, the optimal cutoff value of serum leptin levels as an indicator for predicting of depressive symptoms was projected to be 24.3 ng/mL, which yielded a sensitivity of 88.7 % and a specificity of 73.4 %, with the area under the curve at 0.867 (95 % CI, 0.817-0.916). In multivariate analysis, there was an increased risk of depressive symptoms associated with leptin levels ≥24.3 ng/ml (OR 8.234; 95 % CI, 3.572-15.876; P < 0.0001) after adjusting for possible confounders. Elevated serum leptin levels at delivery could eventually serve as a biological marker for the prediction of depressive symptoms. These associations were independent of other possible variables.

Effect of soothing-liver and nourishing-heart acupuncture on early selective serotonin reuptake inhibitor treatment onset for depressive disorder and related indicators of neuroimmunology: a randomized controlled clinical trial.

OBJECTIVE: To observe the effect of soothing-liver and nourishing-heart acupuncture on selective serotonin reuptake inhibitor (SSRIs) treatment effect onset in patients with depressive disorder and related indicators of neuroimmunology. METHODS: Overall, 126 patients with depressive disorder were randomly divided into a medicine and acupuncture-medicine group using a random number table. Patients were treated for 6 consecutive weeks. The two groups were evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS) and Side Effects Rating Scale (SERS) to assess the effect of the soothing-liver and nourishing-heart acupuncture method on early onset of SSRI treatment effect. Changes in serum 5-hydroxytryptamine (5-HT) and inflammatory cytokines before and after treatment were recorded and compared between the medicine group and the acupuncture-medicine group. RESULTS: The acupuncture-medicine group had significantly lower MADRS scores at weeks 1, 2, 4, and 6 after treatment compared with the medicine group (P < 0.01). The acupuncture group had significantly lower SERS scores at weeks 1, 2, 4, and 6 after treatment compared with the medicine group (P < 0.01). At 6 weeks after treatment, serum 5-HT in the acupuncture-medicine group was significantly higher compared with the medicine group (P < 0.01). Interleukin-6 (IL-6) in the acupuncture-medicine group was significantly lower than that in the medicine group (P < 0.01), whereas there was no significant difference in IL-1ß between the groups (P > 0.05). Anti-inflammatory cytokines IL-4 and IL-10 were significantly higher in the acupuncture-medicine group compared with the medicine group (P < 0.01, P < 0.05, respectively). CONCLUSION: The soothing-liver and nourishing-heart acupuncture method can effectively accelerate the onset of SSRI effects when treating depressive disorder and can significantly reduce the adverse reactions of SSRIs. Moreover, acupuncture can enhance serum 5-HT and regulate the balance of pro-inflammatory cytokines and anti-inflammatory cytokines.

TGF-ß isoforms induce EMT independent migration of ovarian cancer cells.

BACKGROUND: Transforming growth factor beta (TGF-ß) plays major roles in tumorigenesis by regulating cell growth, epithelial-to-mesenchymal transition (EMT), migration/invasion and metastasis. The epithelial markers E-cadherin, claudin-3 and claudin-4, commonly decreased in human adenocarcinomas are actually up regulated during ovarian carcinogenesis. In human ovarian cancer TGF-ß1 may either suppress or promote tumor progression, but whether other TGF-ß isoforms (TGF-ß2 and TGF-ß3) exert similar effects is not known. METHODS: In this study we investigated the ability of the TGF-ß isoforms (TGF-ß1-3) to induce proliferation and migration by BrdU labeling, scratch wound and trans-filter migration assays in the human serous adenocarcinoma cell-line NIH-OVCAR3. Transepithelial resistance was measured and EMT observed by light-microscopy. Expression of adherens-, tight-junction and EMT-related transcription factors was analyzed by qRT-PCR and immunoblotting. RESULTS: All TGF-ß isoforms dose-dependently inhibited NIH-OVCAR3 cell growth, stimulated tumor cell migration with similar efficiency. The mesenchymal marker N-cadherin and claudin-1 expression was induced and occludin down regulated. However, migrating cells retained an epithelial shape and E-cadherin expression. The E-cadherin repressor SNAIL mRNA levels remained low independently of TGF-ß1-3 treatment while ZEB1 expression was enhanced. CONCLUSIONS: TGF-ß1, TGF-ß2 and TGF-ß3 promote migration of NIH-OVCAR3 ovarian cancer cells independently of cell proliferation and without conversion to a complete EMT phenotype. Epithelial ovarian cancer commonly metastasis to the surrounding tissue or inside the peritoneum rather than invading blood vessels to set distance metastasis. Our result raises the question whether ovarian cancer primarily spread via collective migration than via single cell invasion.

Effect of intracavitary electrocardiographic localization on the success rate and complications of PICC in infants.

BACKGROUND: Peripherally inserted central catheter (PICC) is widely used in chemotherapy of children with malignant tumors because of its safe operation and long indwelling time. OBJECTIVE: To investigate the effect of intracavitary electroencephalogram (CEEG) localization technique on the success rate and complications of PICC in infants. METHODS: A total of 180 children with PICC catheterization and maintenance at Shijiazhuang People's Hospital First Hospital from January 2017 to January 2020 were selected and divided into control group (n= 90 cases) and observation group (n= 90 cases). The control group observed the tip position of the fixed catheter through X-ray film and adjusted the catheter until its tip was located in the superior vena cava. The observation group used intracavitary electrocardiogram positioning technology. Comparison of the effects of two groups on the success rate and complications of PICC puncture in infants and young children. RESULTS: The success rate of one puncture in the observation group was significantly higher than that in the control group (P< 0.05). Within one month of catheterization, 13 cases had complications, with an incidence rate of 16.00% lower than the control group's 34.00% (27/80) (P< 0.05). The screening test results showed that the specificity, sensitivity, Youden index, accuracy, kappa coefficient, positive and negative predictive value were 88.89%, 97.56%, 0.86, 96.00%, 0.86, 0.86, respectively. The measured values were 97.56% and 88.89% respectively, and the cost and time of localization were lower than those of X-ray. CONCLUSION: The technique of intracavitary electrogram can be more accurate for infants to place the tip of central venous catheter through peripheral vein, which can effectively improve the success rate of one puncture with low cost, and has high reliability, accuracy and practicability, which is safe and effective.

Sex difference in prebiotics on gut and blood-brain barrier dysfunction underlying stress-induced anxiety and depression.

BACKGROUND: Most of the previous studies have demonstrated the potential antidepressive and anxiolytic role of prebiotic supplement in male subjects, yet few have females enrolled. Herein, we explored whether prebiotics administration during chronic stress prevented depression-like and anxiety-like behavior in a sex-specific manner and the mechanism of behavioral differences caused by sex. METHODS: Female and male C57 BL/J mice on normal diet were supplemented with or without a combination of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) during 3- and 4-week chronic restraint stress (CRS) treatment, respectively. C57 BL/J mice on normal diet without CRS were used as controls. Behavior consequences, gut microbiota, dysfunction of gut and brain-blood barriers, and inflammatory profiles were measured. RESULTS: In the 3rd week, FOS + GOS administration attenuated stress-induced anxiety-like behavior in female, but not in male mice, and the anxiolytic effects in males were observed until the 4th week. However, protective effects of prebiotics on CRS-induced depression were not observed. Changes in the gene expression of tight junction proteins in the distal colon and hippocampus, and decreased number of colon goblet cells following CRS were restored by prebiotics only in females. In both female and male mice, prebiotics alleviated stress-induced BBB dysfunction and elevation in pro-inflammatory cytokines levels, and modulated gut microbiota caused by stress. Furthermore, correlation analysis revealed that anxiety-like behaviors were significantly correlated with levels of pro-inflammatory cytokines and gene expression of tight junction proteins in the hippocampus of female mice, and the abundance of specific gut microbes was also correlated with anxiety-like behaviors, pro-inflammatory cytokines, and gene expression of tight junction proteins in the hippocampus of female mice. CONCLUSION: Female mice were more vulnerable to stress and prebiotics than males. The gut microbiota, gut and blood-brain barrier, and inflammatory response may mediate the protective effects of prebiotics on anxiety-like behaviors in female mice.

PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy--a study in a Swedish rectal cancer trial of preoperative radiotherapy.

BACKGROUND: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients. METHODS: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot. RESULTS: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (P = 0.03). No survival relationship in patients with RT was observed (P = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (P = 0.68)/inner tumour area (P = 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (P = 0.01) CONCLUSIONS: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.

[Efficacy and safety of tandospirone in the treatment of patients with anxiety disorder].

OBJECTIVE: To explore the efficacy and safety of tandospirone for adolescents with anxiety disorder. METHODS: In this multicenter open-label 12-week study, a total of 169 adolescents met the criteria of DSM-IV for anxiety disorder were treated with flexible dose of tandospirone. The effects and safety of treatment were assessed by the Hamilton anxiety scale (HAMA), state-trait anxiety inventory (STAI), clinical global impression (CGI) and side effects at baseline and Weeks 2, 4, 8 and 12. RESULTS: In 151 cases completing the 12-week treatment, the scores of HAMA decreased by 18% ± 12%, 38% ± 16%, 54% ± 20% and 63% ± 17% at Weeks 2, 4, 8 and 12. Significant reductions in HAMA scores were seen at Weeks 2-12 (P < 0.01) and marked improvement appeared in 81.5% cases at Week 12 (reduction rate of HAMA: 50%). At Week 12, the HAMD(17) scores were markedly lower versus baseline (7 ± 2 vs 13 ± 3, P < 0.01). Adverse effect of tandospirone was scarcely found (9.9%). CONCLUSION: Tandospirone is an effective and safe anti-anxiety drug for adolescents.

Woman diagnosed with obsessive-compulsive disorder became delusional after childbirth: A case report.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common mental disorder that varies greatly in manifestation and causes much distress to individuals. We describe a case in which a Chinese woman with OCD became delusional after childbirth, and discuss the possible phenomenological and psychological alterations. CASE SUMMARY: A 27-year-old woman presented to the Psychiatry Department of our hospital with obsessions and compulsions. After taking medication, her symptoms were alleviated. Three years later, during her pregnancy, the obsessions returned and even progressed into paranoid delusions after childbirth. After multiple adjustments of treatment along with several fluctuations, she finally achieved remission and gained reasonable insight. CONCLUSION: This case suggests that the patient with OCD appeared to move along a continuum of beliefs, and highlights the importance of effective intervention during pregnancy, which would exert a significant impact on postpartum exacerbation outcomes.

Current Status of Fear of Disease Progression in Patients with Advanced Cancer and Usefulness of Dignity Therapy Intervention.

With changes in lifestyle and an increase in bad health habits, cancer has become a noncommunicable and frequently occurring disease that poses a serious threat to human life. Cancer is associated with high rates of morbidity and mortality worldwide. As a major negative life event, advanced malignancies lead to strong mood swings in most patients. Furthermore, various internal and external factors can have a huge impact on patients' physical and mental health and put them in a stressful situation, causing a series of psychological stress responses. To explore the degree of fear of disease progression in patients with advanced cancer and the usefulness of dignity therapy. Overall, 120 patients with advanced malignant tumors admitted to Shijiazhuang No. 1 hospital between January 2019 and January 2020 were enrolled. The selected patients were divided into the test and control groups (60 people per group) using a random number table. All patients received basic treatment. Patients in the trial group also received dignity therapy. The intervention period was 4 weeks. Simplified scales were used for assessing disease progression (FoP-Q-SF) and quality of life (QLQ-C30) before and after the intervention, and the scores were compared between the groups. After the intervention, the degree of fear in the experimental group was lower than that of the control group. Cognitive function, emotional function, and the scores of the overall health status of the experimental group were higher than those of the control group. Additionally, the scores of fatigue, insomnia, loss of appetite, and diarrhea in the experimental group were lower than those of the control group (P < 0.05). The social support level scale scores, depression scores, hospital anxiety and depression scale scores, and patient dignity inventory scores of the experimental group were lower than those of the control group (P < 0.05). Patients with advanced malignant tumors have fear, anxiety, and depression related to disease progression. Dignity therapy is useful for improving the patients' quality of life, increasing dignity, and enhancing social support.

Early Effects of Repetitive Transcranial Magnetic Stimulation Combined With Sertraline in Adolescents With First-Episode Major Depressive Disorder.

Background: Adolescence is a period of high incidence for depression. However, there is a limited treatment option for the adolescent depression. For treatment-resistant major depressive disorder, HF-rTMS of the left dorsolateral prefrontal cortex (DLPFC) appears therapeutically effective. The aim of the study is to explore the early effects of repetitive transcranial magnetic stimulation in combination with sertraline in adolescents with first-episode major depressive disorder. Methods: A total of 100 teenage patients with first-episode depression were randomly divided into the study groups. Both groups were treated with sertraline. In addition, the study group was treated with ten sessions of add-on rTMS. The control group was given sertraline only. The depressive symptom and cognitive function were assessed by the Hamilton depression rating scale 17 version (HAMD-17), Children's Depression Rating Scale-Revised (CDRS-R), Integrated visual and auditory continuous performance test (IVA-CPT), and THINC-it. Results: The number of early improvers after 2 weeks of treatment in the study group was statistically significant higher compared to the control group (95.83% vs 73.47%, χ2 = 9.277, P = 0.002). There was significant difference observed in responder rates (62.50% vs. 28.57%, χ2 = 11.262, P = 0.001) or in remission rates (31.25% vs. 6.12%, χ2 = 10.130, P = 0.001) between the two groups at 4 weeks. The score of HAMD-17 and CDRS-R in the study group were significantly lower than the control group (Fgroup = 12.91 vs 10.21, P < 0.05). Attention Quotient (listening, visual and full-scale) attention quotient of IVA-CPT in the study group were higher than those in the control group after treatment, and the differences were statistically significant(P < 0.05). The study group showed higher score in Spotter than the control group after treatment (P < 0.05). Discussion: This is the most extensive blinded, randomized clinical study to date examining the efficacy of 10-Hz add-on rTMS for first-onset adolescent depression. Our results support that add-on rTMS accelerates the efficacy of the antidepressants, improving the depressive symptoms and cold cognitive function in first-episode adolescent depression. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [ChiCTR2100048534].

The Efficacy and Safety of Zaoren Anshen Capsule in Combination with Zolpidem for Insomnia: A Multicentre, Randomized, Double-Blinded, Placebo-Controlled Trial.

Purpose: Insomnia is the most common sleep disorder with high rate of prevalence, persistence, and leads to negative consequences. The mainstays of insomnia treatment have limitations due to either the side effects of hypnotics or limited accessibility to cognitive behavioral therapy. This study aims to compare the efficacy and safety of the traditional Chinese medicine (TCM) Zaoren Anshen capsule alone or as an adjunct treatment with different doses of the nonbenzodiazepine medication zolpidem tartrate in treating insomnia. Method: This randomized, double-blind, multicentre placebo control trial was conducted in 131 patients with chronic insomnia. The patients were randomly assigned to one of the following four regimen groups: Group ZA + Z5 : Zaoren Anshen capsule and 5 mg zolpidem tartrate (n = 32); Group Z5: 5 mg zolpidem tartrate and placebo capsule (n = 35); Group Z10 : 10 mg zolpidem tartrate and placebo capsule (n = 32); Group ZA : Zaoren Anshen capsule and placebo pill (n = 32). The drugs were administered for 4 weeks. All patients were evaluated by the Insomnia Severity Index (ISI) at 0, 2, 4, 5, and 6 weeks, and adverse events were recorded. Result: There are significant differences in the comparison between the four groups at each treatment stage (P < 0.05). Repeated measurement analysis of variance (ANOVA) of ISI scores in each treatment stage of the four groups exhibits significant differences in time effect, intergroup effect, and interaction effect (P < 0.05). After four weeks of drug administration, the treatment efficacy is similar in Groups ZA + Z5 and Z10 (93%) and in Groups Z5 and ZA (62% and 65%, respectively). Groups ZA + Z5 and Z10 present significantly lower ISI scores compared with Groups Z5 and ZA (P < 0.05), which indicates better treatment response of Groups ZA + Z5 and Z10. No significant difference was observed in the incidence of adverse events between the groups. Conclusion: Zaoren Anshen capsule can effectively treat insomnia disorder either alone or in combination with zolpidem tartrate. A preferred combination of TCM Zaoren Anshen capsule with zolpidem can provide a magnified therapeutic efficacy with fewer side effects than zolpidem-only management, clinical trial registration number: Chinese Clinical Trial Registry ChiCTR-IPR-1600969.

Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals.

Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC. Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.

The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers.

RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)(9) at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs {may be a cellular response against tumor from further progression}, while hRAD50 mutation may be involved in the development of MSI CRCs.

MANBA polymorphism was related to increased risk of colorectal cancer in Swedish but not in Chinese populations.

beta-mannosidase, encoded by MANBA, has been suggested to be implicated in cancers, while genetic variations in the MANBA in relation to colorectal cancer (CRC) risk has not been examined. In this study, we investigated the relationship of a polymorphic CA repeat in MANBA gene with CRC risk in 152 Swedish CRC patients and 441 Swedish controls, and 196 Chinese CRC patients and 577 Chinese controls, as well as the clinicopathologic significance of this polymorphism on CRC patients, by using capillary electrophoresis. The MANBA genotypes were related to CRC risk in the Swedish population (p=0.03), but not in the Chinese population. In the Swedish population, individuals with < 22 CAs/< 22 CAs had significantly increased risk for CRC compared with those with >or=22 CAs/>or= 22 CAs (gender-age-adjusted analysis: OR 1.93, 95% CI 1.06-3.51). There was no relationship between the polymorphism and clinicopathologic variables. These findings suggest the different susceptibilities of this polymorphism to CRC development in the two populations.

[Genome-wide screening of predicted sugar transporters in Neurospora crassa and the application in hexose fermentation by Saccharomyces cerevisiae].

The lignocellulolytic filamentous fungus Neurospora crassa is able to assimilate various mono- and oligo-saccharides. However, more than half of predicted sugar transporters in the genome are still waiting for functional elucidation. In this study, system analysis of substrate spectra of predicted sugar transporters in N. crassa was performed at genome-wide level. NCU01868 and NCU08152 have the capability of uptaking various hexose, which are named as NcHXT-1 and NcHXT-2 respectively. Their transport activities for glucose were further confirmed by fluorescence resonance energy transfer analysis. Over-expression of either NcHXT-1 or NcHXT-2 in the null-hexose-transporter yeast EBY.VW4000 restored the growth and ethanol fermentation under submerged fermentation with glucose, galactose, or mannose as the sole carbon source. NcHXT-1/-2 homologues were found in a variety of cellulolytic fungi. Functional identification of two filamentous fungal-conserved hexose transporters NcHXT-1/-2 via genome scanning would represent novel targets for ongoing efforts in engineering cellulolytic fungi and hexose fermentation in yeast.

Identification and characterization of the glucose dual-affinity transport system in Neurospora crassa: pleiotropic roles in nutrient transport, signaling, and carbon catabolite repression.

BACKGROUND: The glucose dual-affinity transport system (low- and high-affinity) is a conserved strategy used by microorganisms to cope with natural fluctuations in nutrient availability in the environment. The glucose-sensing and uptake processes are believed to be tightly associated with cellulase expression regulation in cellulolytic fungi. However, both the identities and functions of the major molecular components of this evolutionarily conserved system in filamentous fungi remain elusive. Here, we systematically identified and characterized the components of the glucose dual-affinity transport system in the model fungus Neurospora crassa. RESULTS: Using RNA sequencing coupled with functional transport analyses, we assigned GLT-1 (Km = 18.42 ± 3.38 mM) and HGT-1/-2 (Km = 16.13 ± 0.95 and 98.97 ± 22.02 µM) to the low- and high-affinity glucose transport systems, respectively. The high-affinity transporters hgt-1/-2 complemented a moderate growth defect under high glucose when glt-1 was deleted. Simultaneous deletion of hgt-1/-2 led to extensive derepression of genes for plant cell wall deconstruction in cells grown on cellulose. The suppression by HGT-1/-2 was connected to both carbon catabolite repression (CCR) and the cyclic adenosine monophosphate-protein kinase A pathway. Alteration of a residue conserved across taxa in hexose transporters resulted in a loss of glucose-transporting function, whereas CCR signal transduction was retained, indicating dual functions for HGT-1/-2 as "transceptors." CONCLUSIONS: In this study, GLT-1 and HGT-1/-2 were identified as the key components of the glucose dual-affinity transport system, which plays diverse roles in glucose transport and carbon metabolism. Given the wide conservation of the glucose dual-affinity transport system across fungal species, the identification of its components and their pleiotropic roles in this study shed important new light on the molecular basis of nutrient transport, signaling, and plant cell wall degradation in fungi.

Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy.

PURPOSE: To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers. METHODS AND MATERIALS: p73 was immunohistochemically examined on biopsies (unirradiated, n=102), distant (from the large bowel, n=82), and adjacent (adjacent to primary tumor, n=89) normal mucosa samples, primary tumors (n=131), and lymph node metastasis (n=32) from rectal cancer patients participating in a clinical trial of preoperative RT. Seventy-four patients received surgery alone and 57 received additional RT. RESULTS: Cytoplasmic p73 was increased in the primary tumor compared with the distant or adjacent mucosa (p

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.