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Background: Diagnosis of congenital syphilis (CS) is not straightforward and can be challenging. This study aimed to evaluate the validity of an algorithm using timing of maternal antisyphilis treatment and titres of non-treponemal antibody as predictors of CS., Methods: Confirmed CS cases and those where CS was excluded were obtained from the Guangzhou Prevention of Mother-to-Child Transmission of syphilis programme between 2011 and 2019. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using receiver operating characteristics (ROC) in two situations: (1) receiving antisyphilis treatment or no-treatment during pregnancy and (2) initiating treatment before 28 gestational weeks (GWs), initiating after 28 GWs or receiving no treatment for syphilis seropositive women., Results: Among 1558 syphilis-exposed children, 39 had confirmed CS. Area under the curve, sensitivity and specificity of maternal non-treponemal titres before treatment and treatment during pregnancy were 0.80, 76.9%, 78.7% and 0.79, 69.2%, 88.7%, respectively, for children with CS. For the algorithm, ROC results showed that PPV and NPV for predicting CS were 37.3% and 96.4% (non-treponemal titres cut-off value 1:8 and no antisyphilis treatment), 9.4% and 100% (non-treponemal titres cut-off value 1:16 and treatment after 28 GWs), 4.2% and 99.5% (non-treponemal titres cut-off value 1:32 and treatment before 28 GWs), respectively., Conclusions: An algorithm using maternal non-treponemal titres and timing of treatment during pregnancy could be an effective strategy to diagnose or rule out CS, especially when the rate of loss to follow-up is high or there are no straightforward diagnostic tools., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To eliminate mother-to-child transmission of syphilis, the Chinese government recommends a treatment regimen that slightly differs from the World Health Organization- (WHO-) recommended treatment. However, little is known about their difference in efficacy. This study is aimed at comparing the effect of China-recommended and WHO-recommend treatment regimens on adverse pregnancy outcomes (APOs) and at examining associated risk factors of APOs among syphilis-seropositive women., Methods: Using the syphilis registry data, we retrospectively collected data from 4488 syphilis-infected pregnant women in Guangzhou during 2011-2018. Multivariate analyses were used to investigate the association between treatment regimens and APOs (ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth or low birth weight, newborn smaller than gestational age, congenital syphilis, and infant death) and the association between risk factors and APOs., Results: Of 3474 participants, 27.3% had at least one APO. Compared to those receiving WHO-recommended treatment, women who received China-recommended treatment were less likely to have APOs (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.38-0.57), whereas those who received no treatment had 1.6 times higher odds of experiencing APOs. One common risk factor across different APOs was high levels of log 2 -transformed toluidine red unheated serum test (TRUST) titers before treatment (OR 1.14, 95% CI 1.10-1.19). China-recommended treatment was effective in reducing APOs for those with TRUST ≥ 1 : 8 (OR 0.21, 95% CI 0.14-0.29) and those with TRUST < 1 : 8 (OR 0.62, 95% CI 0.50-0.77)., Conclusions: Syphilis-seropositive women receiving China-recommended treatment had lower odds of APOs, especially when TRUST titers before treatment were high. Findings can be used to guide health professionals to reduce APOs among syphilis-infected mothers and promote nationwide use of China-recommended treatment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Fang Hu et al.)

Objective: This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children., Methods: This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou, China. The women were assigned to receive combination ART (cART) or mono/dual ART or no treatment. The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth, small for gestational age (SGA)] and adverse early growth outcome (including infant death, HIV infection of mother-to-child transmission, and underweight, wasting and stunting of infants at 4 weeks of age)., Results: Adverse pregnancy outcomes occurred in 202 (35.1%) of all enrolled HIV-infected women, and 121 (31.3%) of all infants exhibited adverse effects on early growth at 4 weeks of age. The rates of adverse pregnancy outcomes, spontaneous abortion, ectopic pregnancy, stillbirth, infant death and perinatal HIV infection were higher among women not receiving ART, compared to those treated with cART or mono/dual ART (P < 0.05). However, women treated with cART had a higher rate of SGA, compared to untreated women (P < 0.05). No differences in early infant growth were observed among the different treatment regimens., Conclusion: Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART, as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival.., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

The present study aimed to investigate the role of semaphorin 4D (Sema4D) in bladder cancer cell proliferation and metastasis in vivo and in vitro. Effects of Sema4D modulation on cancer cell viability and clonogenic abilities were assessed by MTT assay and colony formation assay. Cell apoptosis, cell cycle analysis, transwell assays, and wound-healing assays were also assayed. A mouse model of bladder cancer was established to observe the tumorigenesis in vivo. Our data showed that Sema4D was 4-fold upregulated in clinical bladder cancer tissues relative to noncancerous ones and differentially expressed in bladder cancer cell lines. Knockdown of Sema4D in bladder cancer T24 and 5637 cells significantly decreased cell proliferation, clonogenic potential, and motility. On the contrary, overexpression of Sema4D in bladder cancer SV-HUC-1 cells significantly increased cell viability and motility. Concordantly, knockdown of Sema4D impaired while overexpression of Sema4D promoted bladder cancer cell growth rates in xenotransplanted mice. Cell cycle was arrested by modulation of Sema4D. Cell apoptotic rates and the mitochondrial membrane potentials were consistently increased upon knockdown of Sema4D in T24 cells and 5637 cells. Western blotting revealed that epithelial-mesenchymal transition was promoted by Sema4D. The PI3K/AKT pathway was activated upon Sema4D overexpression in SV-HUC-1 cells, while it was inactivated by knockdown of Sema4D in T24 cells. All these data suggest that Sema4D promotes cell proliferation and metastasis in bladder cancer in vivo and in vitro. The oncogenic behavior of Sema4D is achieved by activating the PI3K/AKT pathway.

Midkine, a heparin-binding growth factor, has been identified as a promising cancer biomarker. In non-small cell lung cancer (NSCLC), the serum and urine midkine levels have not been intensively investigated. The aim of the present study was to investigate the diagnostic and prognostic potential of serum and urine midkine levels in patients with NSCLC. The serum midkine levels were measured in 153 patients with NSCLC, 23 patients with benign pulmonary disease and 95 healthy controls using ELISA. Urine midkine levels were examined in 20 controls and 45 patients with NSCLC. Midkine expression in tumor tissues from 72 patients with NSCLC who underwent definitive surgical resection without any pre-operative treatments was examined by immunohistochemistry. Serum levels were significantly higher in patients with NSCLC than in healthy controls (657.36±496.58 pg/ml vs. 194.49±122.57 pg/ml, P<0.001). As shown in the ROC curve analysis, the sensitivity and specificity of the cut-off serum midkine concentration of 400 pg/ml for predicting the presence of NSCLC were 71.2% and 88.1%, respectively. Positive correlations between the serum midkine levels and immunohistochemistry staining scores (r=0.315, P=0.007) and between the serum midkine levels and urine midkine levels (r=0.636, P<0.001) were observed using Spearman's bivariate correlations. The serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, and its overexpression yielded a relative risk of death of 2.072 (0.01.

Cyclooxygenase-2 (COX-2) is highly expressed in tumor cells and has been regarded as a hallmarker for cancers, but the excise regulatory mechanism of COX-2 in tumorigenesis remains largely unknown. Here, we pulled down and identified a novel COX-2 regulator, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), which could specifically bind to COX-2 core promoter and regulate tumor growth in non-small-cell lung cancers (NSCLCs). Knockdown of hnRNPA2/B1 by shRNA or siRNA downregulated COX-2 expression and prostaglandin E2 (PGE2) production, and suppressed tumor cell growth in NSCLC cells in vitro and in vivo. Conversely, overexpression of hnRNPA2/B1 up-regulated the levels of COX-2 and PGE2 and promoted tumor cell growth. We also showed that hnRNPA2/B1 expression was positively correlated with COX-2 expression in NSCLC cell lines and tumor tissues, and the up-regulated expression of hnRNPA2/B1 and COX-2 predicted worse prognosis in NSCLC patients. Furthermore, we demonstrated that the activation of COX-2 expression by hnRNPA2/B1 was mediated through the cooperation with p300, a transcriptional co-activator, in NSCLC cells. The hnRNPA2/B1 could interact with p300 directly and be acetylated by p300. Exogenous overexpression of p300, but not its histone acetyltransferase (HAT) domain deletion mutation, augmented the acetylation of hnRNPA2/B1 and enhanced its binding on COX-2 promoter, thereby promoted COX-2 expression and lung cancer cell growth. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth by activating COX-2 signaling in NSCLC cells and imply that the hnRNPA2/B1/COX-2 pathway may be a potential therapeutic target for human lung cancers., (Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/β-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3β expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and β-catenin components were all downregulated, whereas GSK-3β was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3β. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/β-catenin signaling pathway, and that this interaction may be mediated by GSK-3β.

Melatonin, a molecule produced throughout the animal and plant kingdoms, and berberine, a plant derived agent, both exhibit antitumor and multiple biological and pharmacological effects, but they have never been combined altogether for the inhibition of human lung cancers. In this study, we investigated the role and underlying mechanisms of melatonin in the regulation of antitumor activity of berberine in lung cancer cells. Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2β and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-κB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2β/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment.

BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.

The present study evaluates the effects of embryonic age and proteolytic enzymes on the isolation and primary culture of chicken enterocyte and to establish an effective technique for chicken intestinal epithelial cell (IEC) cultivation. Fourteen-day-old, 16-day-old and 18-day-old embryos (average weight: 52.23 ± 0.76 g, 50.86 ± 0.99 g, 48.98 ± 1.03 g) were the source for preparation of enterocyte culture, and trypsin-ethylene diamine tetraacetic acid, collagenase, thermolysin and combination of collagenase and thermolysin were used for digestion medium. Optimal culture protocols were determined by qualitative assays of proliferation. Cells isolated by using 14-day-old embryo and collagenase obtain the best attachment and growth in culture, and the production of continuously growing IEC cultures. Thus, we conclude that the use of collagenase as a dissociating enzyme and 14-day-old embryo as a source can be advantageously applied to the isolation of chicken IEC and this method may be useful for various applications and basic studies of the intestinal tract concerning such objects as physiology, immunology and toxicology., (© 2014 Japanese Society of Animal Science.)

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-β (Aβ) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aβ aggregation and attenuating Aβ-induced oxidation in vitro. When given before or after the onset of Aβ deposition via i.p. injection, Edaravone substantially reduces Aβ deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.

Objective: To investigate the expression of mir-16 in lung adenocarcinoma cancer line and to observe the effect of mir-16 on the biological behaviors of human lung adenocarcinoma cancer A549 cell. Methods the expression of mir-16 in A549 cells was examined by quantitative real-time (qRT)-PCR. mir-16 minics was chemically synthesized and transfected into A549 cells by Lipofectamine 2000. The cell cycle and apoptosis changes were assayed by flow cytometry, the cell proliferation was measured by MTS assay. The wild-type and mutant wip1 3'-UTR luciferase reporter rectors were constructed. The relative activity of renila luciferase was detected to confirm the binding site of mir-16 on wip1 mRNA. Results, the expression of mir-16 is reduced in A549 cell compared with the normal bronchial epithelial cell. Transfection of mir-16 minics significantly suppressed the luciferase reporter containing wild type not mutant wip1 3'-UTR. Furthermore enforced expression of mir-16 lead to reduced A549 cell proliferation and promote apoptosis. Conclusion Therapeutic strategies to resume miRNA-16 expression may be benefit to patients with NSCLC in the feature.

Background: To explore the hospitalizations of breast cancer patients undergoing mastectomy, and to provide a basis for management, clinical prevention and treatment., Materials and Methods: We conducted an investigation by means of the retrospective survey and the medical records retrieval system, and made out the data of patients suffered from breast cancer in a hospital in Guangzhou from 2004 to 2013, including age, medical payment methods, pathological type, treatment, treatment results, complications, hospitalization days, cost and so on., Results: The average age of the inpatients was 50.14 years old. The main histologic types were infiltrating duct carcinoma (88.06%). The main surgery was modified radical mastectomy (80.41%). The cure rate was 90.80% during the 10 years. The main medical payment method was self-paying (57.28%). The average hospital stay was 13.51 days, and average hospitalization cost was RMB 23,083.66 yuan, proportion of drug fees up to 39.70%. Postoperative complication rate was 0.79%. The self-paying group was with the highest proportion of drug fees (P<0.05), while the free medical service group was with the longest hospitalization days (P<0.05)., Conclusions: The payment methods significantly affected the proportion of drug fees and hospitalization days. The therapeutic effect was satisfactory with less complications and reasonable proportion of drug fees in our hospital.

Objective: To study the safety, effectiveness and feasibility of suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery (SAU-LEMDS) in the treatment of varicocele., Methods: This study included 80 varicocele patients aged 24 - 44 (mean 28.5 +/- 2.6) years, 25 cases of grade I, 45 cases of grade II and 10 cases of grade III, 58 cases in the left side, 6 in the right and 16 in both sides, and all with asthenospermia. The patients were treated by SAU-LEMDS under subarachnoid anesthesia combined with general anesthesia in a supine position with a head-down-feet-up slope of 15 degrees. Two 5 mm trocars were inserted bilaterally at the umbilical edge, one with a 5 mm 30 degrees laparoscope placed in it, and another into the abdominal cavity below the pubic hairline with a 5 mm laparoendoscopic clipper placed in it. The operation procedure was similar to that of standard laparoscopic ligation of spermatic veins, with reservation of the spermatic artery and double-ligation of spermatic veins. And the procedure was repeated for the contralateral lesion in the bilateral cases. Postoperative follow-up was conducted for the incidences of orchiatrophy and testicular hydrocele and changes of seminal parameters., Results: All the operations were successful, with the mean operation time of (10 +/- 5.0) min (range 8 to 25 min) for the unilateral cases and (18 +/- 6.5) min (range 15 to 30 min) for the bilateral cases, the mean blood loss of (1.5 +/- 0.5) ml (range 1 to 2 ml), and the mean postoperative hospital stay of (2 +/- 0.5) d (range 1.5 to 3 d). The patients were followed up for 6 -24 (12 +/- 2.5) months, which showed significant improvement in sperm motility as compared with the baseline ([28.53 +/- 5.21] vs [19.62 +/- 3.56]%, P < 0.05), with 28 cases (35.0%) restored to normal. Recurrence was found in 4 cases (5.0%). Testicular hydrocele occurred in 7 cases (8.75%), but orchiatrophy in none. The scars in the umbilicus and suprapubis were invisible because of the wrinkles and pubic hair., Conclusion: SAU-LEMDS is safe, effective and feasible for the treatment of varicocele. It is superior to umbilical laparoendoscopic single-site surgery (U-LESS) for its less invasiveness, simpler operation, and better cosmetic appearance.

Objective: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in human esophageal squamous cell carcinoma (ESCC) and its significance., Methods: The expression of VEGF-C mRNA in tumor tissues and non-cancer tissues from 39 ESCC patients in our hospital from March 2009 to February 2010 was detected by in situ hybridization (ISH) method. The expression of D2-40 was detected by immunohistochemistry,and microlymphatic vessel density (MLVD) was determined by lymphatic endothelial specific marker D2-40. The associations of VEGF-C mRNA expression with clinical data and MLVD were analyzed., Results: Positive ISH VEGF-D mRNA was observed in tumor tissue samples of 22 cases (56.4%, 22/39) and non-cancer tissue sample of 1 case (2.6%, 1/39), whose difference was statistically significant (P<0.05). The expression of VEGF-D mRNA in ESCC was significantly associated with lymph node metastasis [92.9% (13/14) vs. 36.0% (9/25), P<0.05] and MLVD [(8.20±1.22) vs. (5.31±0.97), P<0.01], but not significantly associated with age, sex, pathological grade and depth of infiltration., Conclusion: VEGF-D can promote lymphatic metastasis of ESSC by induction of lymphangiogenesis.

Enterovirus 71 (EV71) is one of the major causative agents for hand, foot and mouth disease (HFMD) in childhood. Nowadays, HFMD or EV71 infections have already become an important public health issue throughout the world. Vaccination may be the most effective measure to control the transmission of the virus. Therefore, to pave EV71 vaccine into human clinical trial, in the present study a comprehensive preclinical safety assessment of inactivated EV71 vaccine including single- and repeat-dose toxicity studies were conducted in rats and cynomolgus monkeys. No abnormal findings were observed in rats following single intramuscular administration with EV71 vaccine (640 U). The results also showed no obvious systemic toxicities from four repetitive intramuscular injections, with a 14-d interval, of two dosages of EV71 vaccine in the two animal species. Antinuclear antibody response was not detected after the repeated administrations. Histopathological examination demonstrated the minimal to severe inflammatory changes in muscle tissues of the injection sites in EV71 vaccine-injected animals and most of findings have been improved over time. Furthermore, test article could induce highly EV71-specfic neutralizing antibody response in both animal species. Taken together, these data suggested a favorable safety profile for inactivated EV71 vaccine and supported this product to enter human phase I clinical trial.

Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease. It is axonally transported, endocytosed and sorted to different cellular compartments where amyloid beta (Aβ) is produced. However, the mechanism of APP trafficking remains unclear. We present evidence that huntingtin associated protein 1 (HAP1) may reduce Aβ production by regulating APP trafficking to the non-amyloidogenic pathway. HAP1 and APP are highly colocalized in a number of brain regions, with similar distribution patterns in both mouse and human brains. They are associated with each other, the interacting site is the 371-599 of HAP1. APP is more retained in cis-Golgi, trans-Golgi complex, early endosome and ER-Golgi intermediate compartment in HAP1-/- neurons. HAP1 deletion significantly alters APP endocytosis and reduces the re-insertion of APP into the cytoplasmic membrane. Amyloid precursor protein-YFP(APP-YFP) vesicles in HAP1-/- neurons reveal a decreased trafficking rate and an increased number of motionless vesicles. Knock-down of HAP1 protein in cultured cortical neurons of Alzheimer's disease mouse model increases Aβ levels. Our data suggest that HAP1 regulates APP subcellular trafficking to the non-amyloidogenic pathway and may negatively regulate Aβ production in neurons., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)

Background: Neurons extend their dendrites and axons to build functional neural circuits, which are regulated by both positive and negative signals during development. Brain-derived neurotrophic factor (BDNF) is a positive regulator for neurite outgrowth and neuronal survival but the functions of its precursor (proBDNF) are less characterized., Methodology/principal Findings: Here we show that proBDNF collapses neurite outgrowth in murine dorsal root ganglion (DRG) neurons and cortical neurons by activating RhoA via the p75 neurotrophin receptor (p75NTR). We demonstrated that the receptor proteins for proBDNF, p75NTR and sortilin, were highly expressed in cultured DRG or cortical neurons. ProBDNF caused a dramatic neurite collapse in a dose-dependent manner and this effect was about 500 fold more potent than myelin-associated glycoprotein. Neutralization of endogenous proBDNF by using antibodies enhanced neurite outgrowth in vitro and in vivo, but this effect was lost in p75NTR(-/-) mice. The neurite outgrowth of cortical neurons from p75NTR deficient (p75NTR(-/-)) mice was insensitive to proBDNF. There was a time-dependent reduction of length and number of filopodia in response to proBDNF which was accompanied with a polarized RhoA activation in growth cones. Moreover, proBDNF treatment of cortical neurons resulted in a time-dependent activation of RhoA but not Cdc42 and the effect was absent in p75NTR(-/-) neurons. Rho kinase (ROCK) and the collapsin response mediator protein-2 (CRMP-2) were also involved in the proBDNF action., Conclusions: proBDNF has an opposing role in neurite outgrowth to that of mature BDNF. Our observations suggest that proBDNF collapses neurites outgrowth and filopodial growth cones by activating RhoA through the p75NTR signaling pathway.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. The pathogenesis of AD is not fully understood, and no strong disease-modifying therapies are currently available. Recent studies suggest that the pan-neurotrophin receptor, p75NTR, is a critical factor involved in the pathogenesis of AD. In this review, we have discussed the roles of p75NTR in the production of amyloid-beta (Aβ), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry and cognition decline in AD, and proposed that p75NTR is a potential target for the development of therapeutic drugs for AD. Finally we provide perspectives in developing various therapeutic strategies targeting different aspects of AD hallmarks which relate to p75NTR functions and breaking the p75NTR-mediated positive feedback loop which promotes the cascades in the pathogenesis of AD., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Accumulation of toxic amyloid-β (Aβ) in the cerebral cortex and hippocampus is a major pathological feature of Alzheimer's disease (AD). The neurotrophin receptor p75NTR has been proposed to mediate Aβ-induced neurotoxicity; however, its role in the development of AD remains to be clarified. The p75NTR/ExonIII-/- mice and APPSwe/PS1dE9 mice were crossed to generate transgenic AD mice with deletion of p75NTR gene. In APPSwe/PS1dE9 transgenic mice, p75NTR expression was localized in the basal forebrain neurons and degenerative neurites in neocortex, increased with aging, and further activated by Aβ accumulation. Deletion of the p75NTR gene in APPSwe/PS1dE9 mice reduced soluble Aβ levels in the brain and serum, but increased the accumulation of insoluble Aβ and Aβ plaque formation. There was no change in the levels of amyloid precursor protein (APP) and its proteolytic derivatives, or α-, β-, and γ-secretase activities, or in levels of BACE1, neprilysin (NEP), and insulin-degrading enzyme (IDE) proteins. Aβ production by cortical neurons of APPSwe/PS1dE9 mice was reduced by deletion of p75NTR gene in vitro. Recombinant extracellular domain of p75NTR attenuated the oligomerization and fibrillation of synthetic Aβ(42) peptide in vitro, and reduced local Aβ plaques after hippocampus injection in vivo. In addition, deletion of p75NTR attenuated microgliosis but increased the microhemorrhage profiles in the brain. The deletion of p75NTR did not significantly change the cognitive function of the mice up to the age of 9 months. Our data suggest that p75NTR plays a critical role in regulating Aβ levels by both increasing Aβ production and attenuating its aggregation, and they caution that a therapeutic intervention simply reducing p75NTR may exacerbate AD pathology.

Differential diagnosis for epithelial tissues of normal human gastric, undifferentiation gastric adenocarcinoma, gastric squamous cell carcinomas, and poorly differentiated gastric adenocarcinoma were studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 250 to 650 nm, pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the DNA absorption bands at 260 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 68.5% (p < 0.05), 146.5% (p < 0.05), 282.4% (p < 0.05), 32.4% (p < 0.05), 56.00 (p < 0.05) and 83.0% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the protein absorption bands at 280 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 86.8% (p < 0.05), 262.9% (p < 0.05), 660.1% (p < 0.05) and 34% (p < 0.05), 72. 2% (p < 0.05), 113.5% (p < 0.05) respectively. And pathological changes of gastric epithelial tissues induced that there were significant differences in the averaged value of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log[f(r infinity)] of the carotene absorption bands at 480 nm between epithelial tissues of normal human stomach and human undifferentiation gastric cancer, between epithelial tissues of normal human stomach and human gastric squamous cell carcinomas, and between epithelial tissues of normal human stomach and human poorly differentiated cancer. Their differences were 59.5% (p < 0.05), 73% (p < 0.05), 258.9% (p < 0.05), 118.7% (p < 0.05), 139.2% (p < 0.05), and 324. 6% (p < 0.05) respectively. It is obvious that pathological changes of gastric epithelial tissues induced that there were significant changes in the contents of the DNA, protein and beta-carotene of gastric epithelial tissues. The conclusion can be applied to rapid, low-cost and noninvasive the optical biopsy for gastric cancer and provides a useful reference.

Objective: To identify the significant protein peaks and establish the diagnostic model of myasthenia gravis (MG) by serum proteomics profiling analysis., Methods: The serum samples from 56 MG patients and 16 healthy controls were detected by the technology of surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). The differentially expressed protein peaks were identified to establish a MG diagnostic model. And preliminary validation was performed., Results: Thirty-eight specific protein peaks with significant differences were found in the serum protein pattern of 56 MG patients and 16 healthy controls. Systemic optimization identified 2 protein peaks of M4168.94 and M1122.57. And they were used to build the MG diagnostic model of differentiating 56 cases from 16 controls., Conclusion: The serum protein profiling can be a novel, effective and sensitive tool to screen for MG-related protein peaks and establish a diagnostic model.

Background: The extended thymectomy for myasthenia gravis (MG) is currently available, but in 20% - 40% of the patients the results were not satisfactory. There are no ideal indicators forecasting surgical results before operation. The surface enhanced laser desorption ionization-time of flight-mass spectroscopy (SELDI-TOF-MS) is a currently new technique for detection of protein profiles, and some progresses have been made in cancer diagnosis and efficacy evaluation, but there is no report on efficacy forecasting of MG surgery. This study aimed to establish an efficacy prognosis model for forecasting the efficacy of surgery for MG by analysis of serum protein profiles of MG patients before surgery., Methods: Fifty-six MG patients 6 months after extended thymectomy were enrolled in the study. They were classified into effective or non-effective groups according to symptoms and medication. Their pre-operative blood samples were analyzed for protein profiles by the SELDI-TOF MS technique, and protein peaks were identified for establishment of the efficacy prognosis model of MG surgery. Additional 100 MG patients were subjected to model validation and their pre-operation protein profiles reviewed for post-operative results. The results were compared with those of the post-operative follow-up so as to validate the prognosis model., Results: For the model establishment, symptoms were improved in 33 patients and not improved in 18 patients, with an effective rate of 64.7%. Five (8.9%) patients were lost to follow-up. Within the molecular weight range of 1 000 to 20 000, 3 specific protein peaks were found to be significantly different between the effective and non-effective groups, ie M4110-76, M3394-58, and M1258-55. Using the efficacy prognosis model constructed with these data, the accuracy rate of classification was 87.9% for the effective group, and 83.3% for the non-effective group, with a total accuracy rate of 86.3%. For the model evaluation, 2 (8.9%) patients were lost to follow-up, 62 patients were effective and 36 were non- effective. By comparing with the real results of follow-up with 65 effective and 33 non-effective patients with an effective rate of 66.3%, the accuracy rate of prediction by the prognosis model was 86.2% for the effective group, and was 81.8% for the non-effective group with a total accuracy rate of 84.5%., Conclusions: By protein profiles analysis of pre-operative blood samples taken from MG patients with the SELDI-TOF MS technique, protein peaks correlated with surgery efficacy in MG patients can be found for primary forecasting short-term efficacy of surgery for MG patients.

Differential diagnosis of human colon adenoma was studied using the Kubelka-Munk spectral function of the DNA and protein absorption bands at 260 and 280 nm in vitro. Diffuse reflectance spectra of tissue were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that for the spectral range from 590 to 1 064 nm pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the DNA absorption bands at 260 nm between normal and adenomatous colon epithelial tissues, and the differences were 218% (p < 0.05) and 68.5% (p < 0.05) respectively. Pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the protein absorption bands at 280 nm between normal and adenomatous colon epithelial tissues, and the differences were 208% (p < 0.05) and 59.0% (p < 0.05) respectively. Pathological changes of colon epithelial tissues were induced so that there were significant differences in the averaged values of the Kubelka-Munk function f(r infinity) and logarithmic Kubelka-Munk function log [f(r infinity)] of the beta-carotene absorption bands at 480 nm between normal and adenomatous colon epithelial tissues, and the differences were 41.7% (p < 0.05) and 32.9% (p < 0.05) respectively. Obviously, pathological changes of colon epithelial tissues were induced so that there were significant changes in the contents of the DNA, protein and beta-carotene of colon epithelial tissues. The conclusion can be applied to rapid, low-cost and noninvasive optical biopsy of colon adenoma, and provides a useful reference.

A low-cost, fast, and noninvasive method for early diagnosis of malignant lesions of mucosa tissue based on diffuse reflectance spectra was applied in the study of the optical biopsy of superficial human bladder cancer. In the present paper, differential diagnosis of superficial human bladder cancer was studied using the diffuse reflectance spectral ratio (R540/R575) of the oxygenated hemoglobin absorption bands at 540 and 575 nm in vitro. Diffuse reflectance spectra for mucosa/submucosa tissues of normal bladder and superficial bladder cancer were measured using a spectrophotometer with an integrating sphere attachment. The results of measurement showed that there were three the diffuse reflectance spectral dips at 415, 542 and 577 nm respectively for mucosa/submucosa tissues of normal bladder and superficial bladder cancer in the spectral range from 400 to 600 nm. The mean diffuse reflectance spectral ratio (R540/R575) of normal bladder mucosa/submucosa tissue decreased slowly with time increase after surgical excision, and the mean diffuse reflectance spectral ratio (R540/R575) of superficial bladder cancer mucosa/ submucosa tissue also decreased slowly with time increasing after surgical excision. The mean diffuse reflectance spectral ratios (R540/R575) of normal bladder mucosa/submucosa tissue were 111%, 107%, 104% and 102% after 2, 3, 4 and 5 h after surgical excision respectively, and those of superficial bladder cancer mucosa/submucosa tissue were 98.4%, 95.5%, 93.1% and 91.6% after 2, 3, 4 and 5 h after surgical excision respectively. There were significant differences in mean diffuse reflectance spectral ratio (R540/R575) for mucosa/submucosa tissues between normal bladder and superficial bladder cancer after 2, 3, 4 and 5 h after surgical excision respectively (p < 0.05). Differences in mean diffuse reflectance spectral ratio (R540/R575) for mucosa/ submucosa tissues between normal bladder and superficial bladder cancer were 12.6%, 11.5%, 10.9% and 10.4% after 2, 3, 4 and 5 h after surgical excision respectively. It is obvious that pathological changes in bladder mucosa/submucosa tissues induced changes in the component and structure of the tissues, and especially quantitative changes in oxyhemoglobin and de-oxyhemoglobin of tissues obviously. Conclusion of the study provides a new method that can be applied to rapid, low-cost and noninvasive optical biopsy of superficial bladder cancer.

Objective: To investigate the effect of thoracic duct ligation during transthoracic esophagectomy on preventing post-operative chylothorax in different tumor locations., Methods: Between March 2003 and June 2007, 243 patients with thoracic esophageal carcinoma underwent esophageal resection in our hospital. All the cases were divided into five groups according to tumor localization, including cervical, upper middle, middle, lower middle and lower sections. Each was then subdivided into 2 groups: with and without intraoperative thoracic duct ligation. Statistical analysis was carried out to evaluate the relevance between ligation and non-ligation of the thoracic duct during esophagectomy and the incidence of post-operative chylothorax., Results: A total of 8 cases of post-operative chylothorax was recorded and the incidence was 3.3%. Incidence with respect to tumor location was as follows: cervical section: ligation subgroup 3 cases and non-ligation subgroup 5 cases; upper middle section: no one for both ligation and non-ligation subgroups; middle section: ligation subgroup 0/26 and non-ligation subgroup 1/28 (3.6%); lower middle section: ligation subgroup 1/39 (2.6%) and non-ligation subgroup 1/35 (2.9%); lower section: ligation subgroup 1/37 (2.7%) and non-ligation subgroup 2/44 (4.5%). Logistic regression analysis revealed no significant difference between ligation and non-ligation subgroup in the prevention of post-operative chylothorax (P>0.05)., Conclusion: Thoracic duct ligation as preventive measure can not decrease the incidence of chylothorax secondary to esophagectomy.

Canceration and thermal coagulation of human liver induced changes in the absorption and scattering properties of liver tissue at 710, 730, 750, 77, 790, 810, 830, 850, 870 and 890 nm of Ti: sapphire laser were studied in vitro. The measurements were performed using a double-integrating-sphere setup, and the absorption and scattering properties were assessed from these measurements using the inverse adding-doubling method. The results of measurement showed that canceration of liver induced significant decrease in the absorption coefficients of liver tissue, and the maximum change in the absorption coefficients is 86.12% at 850 nm, while the minimum change in the absorption coefficients is 82.65% at 750 nm. Thermal coagulation of normal liver induced obvious change in the absorption coefficients from 710 to 890 nm, and the maximum change in the absorption coefficients is 79.55% at 710 nm, while the minimum change in the absorption coefficients 0.72% at 790 nm. Thermal coagulation of carcinoma liver tissue induced significant increase in the absorption coefficients, the maximum change in the absorption coefficients of carcinoma liver tissue is 78.69% at 810 nm, in the minimum change in the absorption coefficients of carcinoma liver tissue 38.16% at 710 nm. Canceration of liver induced significant increase in the scattering coefficients of liver tissue, and the maximum change in the scattering coefficients is 158.37% at 710 nm, while the minimum change in the scattering coefficients is 136.03% at 890 nm. Thermal coagulation of normal liver induced significant increase in the scattering coefficients of liver tissue, and the maximum change in the scattering coefficients is 632.92% at 890 nm, while the minimum change for the scattering coefficients is 587.40% at 710 nm. Thermal coagulation of carcinoma liver tissue induced significant increase in the scattering coefficients, and the maximum change in the scattering coefficients of carcinoma liver tissue is 384. 25% at 810 nm, while the minimum change in the scattering coefficients of carcinoma liver tissue is 330. 86% at 710 nm. The change in the absorption and scattering properties also varies with the change of laser wavelength.

Objective: To study the effect of CACNA1H gene mutation G773D on calcium channel function., Methods: By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp technique, we studied the alterations of channel behavior in transfected HEK-293 cells., Results: There were no difference in kinetics of activation and inactivation of calcium channel between wild type and mutant. However comparing with the wild-type Cav3.2 channel, G773D mutant could increase the calcium current density significantly., Conclusion: CACNA1H gene G773D mutation is able to increase calcium current and neuronal excitability.

The preconcentration of trace gallium, germanium, molybdenum and indium by trapping with precipitation of phenylfluorone (PF), and the determination of the elements by GFAAS were developed. The effects such as those of acidity, amounts of PF, aging time, volume of test solution, and the coexistent ions on the preconcentration of the trace elements were examined in detail. The optimum conditions of preconcentration for Ga(III) were pH approximately 2 test solution 500 mL with added 10.00 mg x mL(-1) PF (2.00 mL) and aging for 4 h, those for Ge(IV) were pH approximately 2 test solution 500 mL with added 10.00 mg x mL(-1) PF (4.00 mL) and aging for 10 h, those for Mo(V) were pH approximately 3 test solution 1 000 mL with added 10.00 mg x mL(-1) PF (3.00 mL) and aging for 6 h, and those for In(III) were pH approximately 5 test solution 100 mL with added 10.00 mg x mL(-1) PF (3.00 mL) and aging for 10 h. The experiment results showed that the main contribution to trapping trace gallium, germanium, molybdenum and indium with PF precipitation was post-precipitation instead of coprecipitation. The detection limits (3s) were 0.12 ng x mL(-1) for gallium, 0.30 ng x mL(-1) for germanium, 0.046 ng x mL(-1) for molybdenum and 2.7 ng x mL(-1) for indium. The developed methods were successfully applied to the determination of trace amount of the elements in water samples, geological standard reference materials, and zinc concentrate samples by graphite furnace atomic absorption spectrometry.

The purpose of the study is to analyze and compare differences in the optical properties between normal and adenomatous human colon tissues in vitro at 630-, 680-, 720-, 780-, 850-, and 890-nm wavelengths using a Ti:sapphire laser. The optical parameters of tissue samples are determined using a double integrating sphere setup at seven different laser wavelengths. The inverse Monte Carlo simulation is used to determine the optical properties from the measurements. The results of measurement show that the optical properties and their differences vary with a change of laser wavelength for normal and adenomatous colon mucosa/submucosa and normal and adenomatous colon muscle layer/chorion. The maximum absorption coefficients for normal and adenomatous human colon mucosa/submucosa are 680 nm, and the minimum absorption coefficients for both are 890 nm. The maximum difference of the absorption coefficients between both is 56.8% at 780 nm. The maximum scattering coefficients for normal and adenomatous colon mucosa/submucosa are 890 nm, and the minimum scattering coefficients for both are 780 nm. The maximum difference of the scattering coefficients between both is 10.6% at 780 nm. The maximum absorption coefficients for normal and adenomatous colon muscle layer/chorion are 680 nm, and the minimum absorption coefficients for both are 890 nm. The maximum difference of the absorption coefficients between both is 47.9% at 780 nm. The maximum scattering coefficients for normal and adenomatous colon muscle layer/chorion are 890 nm, and the minimum scattering coefficients for both are 680 nm. The maximum difference of the scattering coefficients between both is 9.61% at 850 nm. The differences in absorption coefficients between normal and adenomatous tissues are more significant than those in scattering coefficients.

Aim: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods., Methods: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integrating-sphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable., Results: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength, and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength. There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa, and there were also large differences in these value ranges between both colon muscle layer/chorion. There are the same orders of magnitude in the absorption coefficients for four kinds of colon tissues. The scattering coefficients of these tissues exceed the absorption coefficients by at least two orders of magnitude., Conclusion: There were large differences in the three optical parameters between normal and adenomatous human colon mucosa/submucosa at the same laser wavelength, and there were also large differences in these parameters between both colon muscle layer/chorion at the same laser wavelength. Large differences in optical parameters indicate that there were large differences in compositions and structures between both colon mucosa/submucosa, and between both colon muscle layer/chorion. Optical parameters for four kinds of colon tissues are wavelength dependent, and these differences would be useful and helpful in clinical applications of laser and tumors photodynamic therapy (PDT).