We demonstrate a technique to determine the Van der Waals radius of iodine atoms using Raman spectroscopy. The iodine diatomic molecules are diffused into the nano-scale channels of a zeolite single crystal. We found their polarized Raman spectroscopy, which corresponds to iodine molecule's vibrational motion along the direction of molecular axis, is significantly modified by the interaction between the iodine molecules and the rigid frame of the crystal's nano-channels. From the number of excitable vibration quantum states of the confined iodine molecules determined from Raman spectra and the size of the nano-channels, we estimate the iodine atomic radius to be 2.10 ± 0.05 Å. It is the first time that atomic sizes, which are far beyond the optical diffraction limit, have be resolved optically using Raman spectroscopy with the help of nano-scale structures.
The ATP synthase consists of two opposing rotary motors, F0 and F1, coupled to each other. When the F1 motor is not coupled to the F0 motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F1-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F1-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F1-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F1 motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F1 motor, which increases the motor’s rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F1 motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F1 motor and provide insight about the stochastic wave mechanics of F1-ATPase.
F1-ATPase; Molecular motor; Chemo-mechanic coupling; Nonlinearity; Dynamics
The neurohypophysis is a crucial component of the hypothalamo-pituitary axis, serving as the site of release of hypothalamic neurohormones into a plexus of hypophyseal capillaries. The growth of hypothalamic axons and capillaries to the forming neurohypophysis in embryogenesis is therefore crucial to future adult homeostasis. Using ex vivo analyses in chick and in vivo analyses in mutant and transgenic zebrafish, we show that Fgf10 and Fgf3 secreted from the forming neurohypophysis exert direct guidance effects on hypothalamic neurosecretory axons. Simultaneously, they promote hypophyseal vascularisation, exerting early direct effects on endothelial cells that are subsequently complemented by indirect effects. Together, our studies suggest a model for the integrated neurohemal wiring of the hypothalamo-neurohypophyseal axis.
FGF; Guidance; Hypothalamus; Zebrafish; Chick
More than 30 prostate cancer (PCa) risk-associated loci have been identified in populations of European descent by genome-wide association studies (GWAS). We hypothesized that a subset of these loci may be associated with PCa risk in Chinese men. To test this hypothesis, 33 single nucleotide polymorphisms (SNPs), one each from the 33 independent PCa risk-associated loci reported in populations of European descent, were investigated for their associations with PCa risk in a case-control study of Chinese men (1,108 cases and 1,525 controls). We found that 11 of the 33 SNPs were significantly associated with PCa risk in Chinese men (P < 0.05). The reported risk alleles were associated with increased risk for PCa, with allelic odds ratios ranging from 1.12 to 1.44. The most significant locus was located on 8q24 Region 2 (rs16901979, P = 5.14×10−9) with a genome-wide significance (P < 10−8), and three loci reached the Bonferroni correction significance level (P < 1.52×10−3), including 8q24 Region 1 (rs1447295, P = 7.04×10−6), 8q24 Region 5 (rs10086908, P = 9.24×10−4), and 8p21 (rs1512268, P = 9.39×10−4). Our results suggest that a subset of the PCa risk-associated SNPs discovered by GWAS among men of European descent is also associated with PCa risk in Chinese men. This finding provides evidence of ethnic differences and similarity in genetic susceptibility to PCa. GWAS in Chinese men are needed to identify Chinese-specific PCa risk-associated SNPs.
AIM: To evaluate the safety and efficacy of granulocyte-colony stimulating factor (G-CSF) therapy in patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF).
METHODS: Fifty-five patients with HBV-associated ACLF were randomized into two groups: the treatment group and the control group. Twenty-seven patients in the treatment group received G-CSF (5 μg/kg per day, six doses) treatment plus standard therapy, and 28 patients in the control group received standard therapy only. The peripheral CD34+ cell count was measured consecutively by flow cytometry. Circulating white blood cell count, biochemical parameters, and other clinical data of these patients were recorded and analyzed. All patients were followed up for a period of 3 mo to evaluate the changes in liver function and survival rate.
RESULTS: The peripheral neutrophil and CD34+ cell counts in the G-CSF group increased on day 3 from the onset of therapy, continued to rise on day 7, and remained elevated on day 15 compared to those of the control group. Child-Turcotte-Pugh score of patients in the treatment group was improved on day 30 from the onset of G-CSF therapy, compared to that in the controls (P = 0.041). Model for End-Stage of Liver Disease score of patients in the treatment group was improved on day 7 (P = 0.004) and remained high on day 30 from the onset of G-CSF therapy (P < 0.001) compared to that in controls. After 3 mo of follow-up observation, the survival rate in the treatment group (48.1%) was significantly higher than that in the control group (21.4%) (P = 0.0181).
CONCLUSION: G-CSF therapy promoted CD34+ cell mobilization in patients with HBV-associated ACLF, and improved the liver function and the survival rate of these patients.
Acute-on-chronic liver failure; Granulocyte-colony stimulating factor; Hepatitis B virus
Nitric oxide (NO) has been known to preserve the level of chlorophyll (Chl) during leaf senescence. However, the mechanism by which NO regulates Chl breakdown remains unknown. Here we report that NO negatively regulates the activities of Chl catabolic enzymes during dark-induced leaf senescence. The transcriptional levels of the major enzyme genes involving Chl breakdown pathway except for RED CHL CATABOLITE REDUCTASE (RCCR) were dramatically up-regulated during dark-induced Chl degradation in the leaves of Arabidopsis NO-deficient mutant nos1/noa1 that exhibited an early-senescence phenotype. The activity of pheide a oxygenase (PAO) was higher in the dark-induced senescent leaves of nos1/noa1 compared with wild type. Furthermore, the knockout of PAO in nos1/noa1 background led to pheide a accumulation in the double mutant pao1 nos1/noa1, which retained the level of Chl during dark-induced leaf senescence. The accumulated pheide a in darkened leaves of pao1 nos1/noa1 was likely to inhibit the senescence-activated transcriptional levels of Chl catabolic genes as a feed-back inhibitory effect. We also found that NO deficiency led to decrease in the stability of photosynthetic complexes in thylakoid membranes. Importantly, the accumulation of pheide a caused by PAO mutations in combination with NO deficiency had a synergistic effect on the stability loss of thylakoid membrane complexes in the double mutant pao1 nos1/noa1 during dark-induced leaf senescence. Taken together, our findings have demonstrated that NO is a novel negative regulator of Chl catabolic pathway and positively functions in maintaining the stability of thylakoid membranes during leaf senescence.
To examine the effect of rimonabant on neurocognitive impairments in people with schizophrenia.
Participants entered a 16-week double-blind, placebo-controlled, randomized clinical trial. A neurocognitive battery was administered at baseline and end of study.
In comparison to rimonabant (20mg/day), placebo-treated participants exhibited a significant improvement on the Repeatable Battery for the Assessment of Neuropsychological Status total score. In contrast, rimonabant was associated with significant improvement on a probabilistic learning task. There were no other significant treatment effects.
Rimonabant did not improve global cognitive functioning, but did improve a specific learning deficit based on response to positive feedback.
rimonabant; cognition; schizophrenia; CB1 receptor antagonist; probabilistic learning
A recent genome-wide association study has identified five new genetic variants for prostate cancer susceptibility in a Japanese population, but it is unknown whether these newly identified variants are associated with prostate cancer risk in other populations, including Chinese men. We genotyped these five variants in a case–control study of 1524 patients diagnosed with prostate cancer and 2169 control subjects from the Chinese Consortium for Prostate Cancer Genetics (ChinaPCa). We found that three of the five genetic variants were associated with prostate cancer risk (P = 4.33 × 10−8 for rs12653946 at 5p15, 4.43 × 10−5 for rs339331 at 6q22 and 8.42 × 10−4 for rs9600079 at 13q22, respectively). A cumulative effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (Ptrend = 2.58 × 10−13), and men with 5–6 risk alleles had a 2-fold higher risk of prostate cancer than men with 0–2 risk alleles (odds ratio = 2.26, 95% confidence interval = 1.78–2.87). Furthermore, rs339331 T allele was significantly associated with RFX6 and GPRC6A higher messenger RNA expression, compared with the C allele. However, none of the variants was associated with clinical stage, Gleason score or family history. These results provide further evidence that the risk loci identified in Japanese men also contribute to prostate cancer susceptibility in Chinese men.
The conserved domain of bacteria-derived flagellin coupling Toll-like receptor 5 (TLR5) activates NF-κB and MAPK signaling transductions, which subsequently regulate the transcription and expression of genes encoding immune mediators. However, whether the flagellin binding monoclonal antibody (MAb) obstructs TLR5-associated signaling is unclear. Here we report on the production and characterization of MAb 5G10 that specifically recognizes flagellin. The MAb 5G10 was produced by the hybridization of mouse myeloma cell SP2/0 with splenocyte from a flagellin immunized BALB/c mouse. We observed that deletion of the conserved amino acid residues 89-96 made flagellin lose its capacity for binding 5G10. Additionally, MAb 5G10 remarkably suppressed the expression of cytokine IL8 of Caco-2 cell by blocking the flagellin-TLR5 signaling. Furthermore, this MAb would be useful for cytosolic localization of flagellin and would facilitate the elucidation of the physiological function of specific pathogen-associated molecular patterns.
Bacillus atrophaeus C89, isolated from the marine sponge Dysidea avara, is a potential producer of bioactive compounds, such as neobacillamide A and bacillamide C. Here, we present a 4.2-Mb assembly of its genome. The nonribosomal peptide synthetases (NRPSs) make it possible to produce the bioactive compounds.
Mesenchymal stem cells (MSCs) can suppress dendritic cells (DCs) maturation and function, mediated by soluble factors, such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), and nitric oxide (NO). Interleukin-10 (IL-10) is a common immunosuppressive cytokine, and the downstream signaling of the JAK-STAT pathway has been shown to be involved with DCs differentiation and maturation in the context of cancer. Whether IL-10 and/or the JAK-STAT pathway play a role in the inhibitory effect of MSCs on DCs maturation remains controversial. In our study, we cultured MSCs and DCs derived from rat bone marrow under different culturing conditions. Using Transwell plates, we detected by ELISA that the level of IL-10 significantly increased in the supernatants of MSC-DC co-cultures at 48 hours. The cell immunofluorescence assay suggested that the MSCs secreted more IL-10 than the DCs in the co-cultures. Adding exogenous IL-10 to the DCs monoculture or MSC-DC co-cultures stimulated IL-10 and led to a decrease in IL-12, and lower expression of the DCs surface markers CD80, CD86, OX62, MHC-II and CD11b/c. Supplementing the culture with an IL-10 neutralizing antibody (IL-10NA) showed precisely the opposite effect of adding IL-10. Moreover, we demonstrated that the JAK-STAT signaling pathway is involved in inhibiting DCs maturation. Both JAK1 and STAT3 expression and IL-10 secretion decreased markedly after adding a JAK inhibitor (AG490) to the co-culture plate. We propose that there is an IL-10 positive feedback loop, which may explain our observations of elevated IL-10 and enhanced JAK1 and STAT3 expression. Overall, we demonstrated that MSCs inhibit the maturation of DCs through the stimulation of IL-10 secretion, and by activating the JAK1 and STAT3 signaling pathway.
Colorectal cancer is a leading cause of cancer mortality in both developed and developing countries. Transforming basic research results into clinical practice is one of the key tasks of translational research, which will greatly improve the diagnosis and treatments of colorectal cancer. In this paper, a translational research platform for colorectal cancer, named crcTRP, is introduced. crcTRP serves the colorectal cancer translational research by providing various types of biomedical information related with colorectal cancer to the community. The information, including clinical data, epidemiology data, individual omics data, and public omics data, was collected through a multisource biomedical information collection solution and then integrated in a clinic-omics database, which was constructed with EAV-ER model for flexibility and efficiency. A preliminary exploration of conducting translational research on crcTRP was implemented and worked out a set of clinic-genomic relations, linking clinical data with genomic data. These relations have also been applied to crcTRP to make it more conductive for cancer translational research.
Histiocytic sarcoma (HS) is a rare malignant neoplasm that originates from a histiocytic hematopoietic lineage characterized by histiocytic differentiation and its corresponding immunophenotypic features. We herein reported a case of primary HS of the stomach which was confirmed through histopathologic examination and immunohistochemical staining. A 52-year-old woman presented with progressive difficulty in feeding and dull pain in the epigastric region. Gastroscopy, endoscopic ultrasonography, double contrast examination, and computed tomography revealed a mass located on the posterior wall of fundus and lesser curvature of the stomach. Microscopically, the cytoplasm of the tumor cells was abundant and eosinophilic. Immunohistochemical staining revealed that the tumor cells were positive for CD45RO and CD68. It is difficult to differentiate HS of stomach from other gastric malignancies by radiological evaluation alone. However, HS may be considered when a protruding and ulcerated mass in stomach shows heterogeneous hypervascular features. To the best of our knowledge, this is the first report in English language literature that emphasizes the imaging findings of human gastric HS.
Histiocytic sarcoma; Stomach; Primary; Endoscopic ultrasonography; Gastroscope; Double contrast examination; Computed tomography
CD44, a transmembrane glycoprotein, is a major receptor for extracellular proteins involved in invasion and metastasis of human cancers. We have previously demonstrated that the novel Gemini vitamin D analog BXL0124 [1α,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluro-cholecalciferol] repressed CD44 expression in MCF10DCIS.com basal-like human breast cancer cells and inhibited MCF10DCIS xenograft tumor growth. In the present study, we investigated potential factors downstream of CD44 and the biological role of CD44 repression by BXL0124 in MCF10DCIS cells.
Methods and Findings
The treatment with Gemini vitamin D BXL0124 decreased CD44 protein level, suppressed STAT3 signaling, and inhibited invasion and proliferation of MCF10DCIS cells. The interaction between CD44 and STAT3 was determined by co-immunoprecipitation. CD44 forms a complex with STAT3 and Janus kinase 2 (JAK2) to activate STAT3 signaling, which was inhibited by BXL0124 in MCF10DCIS cells. The role of CD44 in STAT3 signaling and invasion of MCF10DCIS cells was further determined by the knockdown of CD44 using small hairpin RNA in vitro and in vivo. MCF10DCIS cell invasion was markedly decreased by the knockdown of CD44 in vitro. The knockdown of CD44 also significantly decreased mRNA expression levels of invasion markers, matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA), in MCF10DCIS cells. In MCF10DCIS xenograft tumors, CD44 knockdown decreased tumor size and weight as well as invasion markers.
The present study identifies STAT3 as an important signaling molecule interacting with CD44 and demonstrates the essential role of CD44-STAT3 signaling in breast cancer invasion. It also suggests that repression of CD44-STAT3 signaling is a key molecular mechanism in the inhibition of breast cancer invasion by the Gemini vitamin D analog BXL0124.
Salmonella typhimurium double leu-arg auxotrophs have been shown to be highly effective as antitumor agents in nude mouse models of human metastatic cancer. In order to proceed to clinical development of the S. typhimurium double auxotroph, termed A1-R, it is necessary to evaluate antitumor efficacy in immunocompetent mice. In the present study, we have observed the efficacy of A1-R on the Lewis lung (LLC) carcinoma in vitro as well as in C57BL/6 (C57) immunocompetent mice. In vitro, A1-R treatment of LLC began to induce cell death within one hour. Various doses and schedules of A1-R were administered to C57 mice implanted with LLC, including bolus single intravenous injection; medium dose with weekly intravenous administration and metronomic treatment with small intravenous doses twice a week. Bolus treatment was toxic to the immunocompetent host in contrast to nude mice. Lower-dose weekly doses and metronomic doses were well-tolerated by the immunocompetent host. Weekly intravenous injection with 2 × 107 bacteria and twice a week intravenous injection with 107 bacteria significantly inhibited metastasis formation, while bolus injection was toxic. Intrathoracic administration was performed with 108 A1-R bacteria injected into Lewis lung-bearing C57 mice weekly for three weeks. Lung metastasis was significantly inhibited by intrathoracic bacterial administration without toxicity. The results in this report, demonstrating the anti-metastatic efficacy of S. typhimurium A1-R in immunocompetent mice, indicate the clinical potential of bacterial therapy of cancer.
Salmonella typhimurium; amino acid auxotroph; selective tumor targeting; lung; metastasis; RFP; GFP; fluorescence imaging; confocal microscopy
Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.
cancer stem cells; gastric adenocarcinoma; CD44; CD54; circulating tumor cells
The differential diagnosis between idiopathic nonspecific interstitial pneumonia(INSIP) and idiopathic pulmonary fibrosis(IPF)/usual interstitial pneumonia(UIP)is tough in both clinicians and pathologists. In this study, we analyzed the lesions of right lung removed from a 58-year-old patient by gross and microscopy. The results showed that the pathological appearance of nonspecific interstitial pneumonia (NSIP) and UIP coexisted in his upper lobe. Besides, because of severe fibrosis in middle and lower lobes, it was hard to distinguish the lesions of NSIP fibrotic pattern (NSIP-F) or UIP. Based on clinic-radiologic-pathological data, the diagnosis of INSIP-F was made for this patient finally. Our study suggests that UIP is not always an accurate diagnosis when the NSIP and UIP coexist, and NSIP can have regions of UIP.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2573531681608730
Nonspecific interstitial pneumonia; Usual interstitial pneumonia; Idiopathic nonspecific interstitial pneumonia; Diagnosis
Translational Science Search (http://tscience.nlm.nih.gov) is a Web application for finding MEDLINE/PubMed journal articles that are regarded by their authors as novel, promising, or may have potential clinical application. A set of “translational” filters and related terms was created by reviewing journal articles published in clinical and translational science journals. Through E-Utilities, a user’s query and translational science (TS) filters are submitted to PubMed, and then the retrieved PubMed citations are matched with a database of MeSH terms (for disease conditions) and RxNorm (for interventions) to locate the search term, translational filters found, and associated interventions in the title and abstract. An algorithm ranks the Interventions and Conditions, and then highlights them in the results page for quick reading and evaluation. Using previously searched terms and standard formulas, the Precision and Recall of Translational Science Search (TSS) were 0.99 and 0.47, compared to 0.58 and 1.0 for PubMed Entrez, respectively.
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with genomic aberrations has been shown to resemble lymphoma-type adult T-cell leukemia/lymphoma (ATLL) in terms of its genomic aberration patterns, histopathology, and prognosis. We have shown recently that a majority of patients with acute-type ATLL have multiple subclones that were likely produced in lymph nodes. In this study, we analyzed whether PTCL, NOS with genomic aberrations also has multiple subclones as found in ATLL by means of high-resolution oligo-array comparative genomic hybridization (CGH). Thirteen cases of PTCL, NOS were available for 44K high-resolution array CGH analysis. The results showed that 11 (84.6%) of the 13 cases had a log2 ratio imbalance, suggesting that multiple subclones exist in PTCL, NOS with genomic aberrations. In order to analyze the association between multiple subclones and prognosis, we used previous bacterial-artificial chromosome (BAC) array analyses for 29 cases and found that the existence of multiple subclones was associated with a poor prognosis (P = 0.0279).
Multiple subclones, not otherwise specified; oligo-array comparative genomic hybridization; peripheral T-cell lymphoma
To investigate whether Gli1 expression is important in relapse after radical operation of breast cancer.
Using immunohistochemistry, Gli1 expression was analyzed in human primary breast cancer (n=284) and paracancerous tissues (n=20), and also in local lymph nodes (n=28) and metastatic lymph nodes (n=28).
Initial analysis of Gli1 expression in a small cohort of 20 breast tumors and their paracancerous tissues showed a tendency towards Gli1 overexpression in breast cancer tissues (P<0.001). Further, Gli1 expression in 284 breast cancer tissue samples was analyzed and a significant correlation was found between increased expression of nuclear Gli1 and unfavorable recurrence-free survival (RFS) (P<0.05). The nuclear expression of Gli1 in metastatic lymph nodes following relapse after radical operation was much higher than that in the local lymph nodes of primary carcinoma (P<0.05). Most interestingly, the expression of Gli1 was much higher in the interstitial tissues of the relapsed group than of the non-relapsed group (P<0.001).
Breast cancer shows a high prevalence of Gli1 expression, which is significantly correlated with aggressive features and unfavorable RFS. Nuclear Gli1 overexpression, especially in the interstitial tissues, signified early relapse after radical operation of breast cancer.
Gli1; prognosis; breast cancer
Accumulated evidence has suggested that potentiation of cortical GABAergic inhibitory neurotransmission may be a key mechanism in the treatment of schizophrenia. However, the downstream molecular mechanisms related to GABA potentiation remain unexplored. Recent studies have suggested that dopamine D2 receptor antagonists, which are used in the clinical treatment of schizophrenia, modulate protein kinase B (Akt)/glycogen synthase kinase (GSK)-3 signaling. Here we report that activation of GABAB receptors significantly inhibits Akt/GSK-3 signaling in a β-arrestin-dependent pathway. Agonist stimulation of GABAB receptors enhances the phosphorylation of Akt (Thr-308) and enhances the phosphorylation of GSK-3α (Ser-21)/β (Ser-9) in both HEK-293T cells expressing GABAB receptors and rat hippocampal slices. Furthermore, knocking down the expression of β-arrestin2 using siRNA abolishes the GABAB receptor-mediated modulation of GSK-3 signaling. Our data may help to identify potentially novel targets through which GABAB receptor agents may exert therapeutic effects in the treatment of schizophrenia.
Microtubules play extensive roles in cellular processes, including cell motility. Stathmin is an important protein which destabilizes microtubules. The essential function of stathmin is closely associated with its phosphorylation status. Stathmin is overexpressed in many human cancers and has a significant relationship with clinical characteristics such as grade, tumor size and prognosis. We demonstrated that stathmin was overexpressed in ESCC tissues using both 2-DE and immunohistochemistry analysis. In addition, overexpression of stathmin was significantly correlated with histological grade in ESCC. However, no correlation was found with age, gender and lymph node metastasis. Knockdown of stathmin with siRNA impaired cell migration in KYSE30 and KYSE410 cells. When EC0156 cells were treated with paclitaxel, stathmin was stably phosphorylated and migration was impaired. These observations suggest that stathmin may have a more important function in ESCC development and migration. The present study provides further understanding of the importance of stathmin in ESCC therapy or diagnosis.
stathmin; esophageal squamous cell carcinoma; migration; phosphorylation
To date, the useful markers of hepatocellular carcinoma (HCC) remains incompletely developed. Here, we show that annexin A2 complement alpha-fetoprotein (AFP), a widely used liver cancer marker, in the serologically surveillance and early detection of HCC. First, differentially expressed proteins in HCC were identified using a subcellular proteomic approach. Annexin A2 was then selected for further verification. It was found to be overexpressed in HCC tissues (60.7%, 136/224). Using a self-estabished sandwich enzyme-linked immunosorbent assay, we found that annexin A2 significantly increased in the sera of HCC (n = 175, median, 24.75ng/µl) compared with the healthy (n = 49, median, 16.69ng/µl), benign tumors (n = 19, median, 19.92ng/µl), hepatitis (n = 23, median, 6.48ng/µl) and cirrhosis (n = 51, median, 7.39ng/µl) controls and other malignant tumors (n = 87). Importantly, raised concentrations of annexin A2 were observed in 83.2% (79/95) of early stage (median, 24.32ng/µl) and 78.4% (58/74) of AFP-negative (median, 24.09ng/µl) patients. Annexin A2 alone had a better area under the receiver-operating characteristic curve (AUC = 0.79, 95% confidence interval: 0.73–0.85) in comparison with AFP (AUC = 0.73, 95% confidence interval: 0.66–0.80) in detecting of early stage HCC. Combining both markers notably improved the diagnostic efficiency of early HCC with an achieved sensitivity of 87.4%. Additionally, the expression characteristics of annexin A2 during hepatocarcinogenesis were detected in p21-HBx gene knockin transgenic mice model. The results showed that annexin A2 expression was substantially elevated in HCC-bearing mice, in accordance with the finding in human samples. In conclusion, annexin A2 may be an independent serological candidate for hepatitis B virus–related HCC, especially in the early stage cases with normal serum AFP.
To define the sites where the lateral femoral cutaneous nerve (LFCN) is more easily visualized and to describe the anatomical variations of the LFCN.
A total of 240 LFCNs in 120 volunteers were evaluated with 18 MHz ultrasound; the intermuscular space between the tensor fasciae latae muscle and the sartorius was used as an initial sonographic landmark. The time taken to identify the nerve was recorded. The number of nerve branches at the level of the inguinal ligament (IL) and the relationship between the LFCN and the IL was assessed. The nerve cross-sectional area (CSA) of the LFCN and the distance between the LFCN and the anterior superior iliac spine was measured.
Each nerve was identified using ultrasound in all participants. The mean time for identifying the nerve was 7s for unilateral LFCNs. The nerve passed under the IL in 198 cases, whereas in 44 cases, it passed through to the IL. The LFCN consisted of 1–4 branches just after its passage under or through the IL. The CSA of the LFCN was 1.04±0.44 mm2, and the mean distance between the LFCN and the anterior superior iliac spine was 15.6 ± 4.2 mm.
It is easier to identify the LFCN if the intermuscular space between the tensor fasciae latae muscle and the sartorius is used as an initial sonographic landmark. The anatomical variation of the LFCN can be viewed with high-frequency ultrasound.
Ultrasound; Lateral femoral cutaneous nerve; Inguinal ligament; Anatomy
It is of great interest to identify new neurons in the adult human brain, but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial. In the present study, we have described the general configuration of the RMS in adult monkey, fetal human and adult human brains. We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain. The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin, polysialylated neural cell adhesion molecule and βIII-tubulin. Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS, indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ. Interestingly, no neuroblasts are found in the adult human olfactory bulb. Taken together, our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.
human; rhesus monkey; stem cells; neurogenesis; neuroblasts; subventricular zone; rostral migratory stream