Search

Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC)., Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3., Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro., Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown., Patients and Methods: This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments., Results: In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells., Conclusion: Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells., Competing Interests: The authors declare no competing financial interests or no personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Yang et al.)

Noise interference has become a common health risk in population-densified urban areas where social noise occurs frequently. However, the influence of an individual's perception of social noise exposure risk on reactive behavior remains unknown. This study developed an integrative psychosocial perspective-based model that includes constructs from two theoretical frameworks (the Theory of Planned Behavior and the Value-Belief-Norm theory) to analyze noise risk perception and behavioral intention for social noise mitigation. Haidian District, Beijing, was selected as the case study area and 300 questionnaires were distributed. The results showed that personal attributes had significant effects on residents' noise exposure risk perception and noise-mitigation behavioral intentions. Noise perception, as represented by awareness of consequences and ascription of responsibility, was significantly related to noise mitigation behavioral intention. Awareness of consequences directly positively influenced behavioral intention (β = 0.235, p < 0.001) and indirectly positively influenced behavioral intention through the mediating effect of the ascription of responsibility, which accounted for 24 % of the total effect of awareness of consequences on behavioral intention. This study provides valuable insights into the risks of social noise and encourages adaptive measures to reduce it., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Peng Ru reports financial support was provided by Ministry of Science and Technology. Chunyan Wang reports financial support was provided by Ministry of Science and Technology. Peng Ru reports financial support was provided by National Natural Science Foundation of China. Chunyan Wang reports financial support was provided by National Natural Science Foundation of China., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Cassava is a crucial crop that makes a significant contribution to ensuring human food security. However, high-quality telomere-to-telomere cassava genomes have not been available up to now, which has restricted the progress of haploid molecular breeding for cassava. In this study, we constructed two nearly complete haploid resolved genomes and an integrated, telomere-to-telomere gap-free reference genome of an excellent cassava variety, 'Xinxuan 048', thereby providing a new high-quality genomic resource. Furthermore, the evolutionary history of several species within the Euphorbiaceae family was revealed. Through comparative analysis of haploid genomes, it was found that two haploid genomes had extensive differences in linear structure, transcriptome features, and epigenetic characteristics. Genes located within the highly divergent regions and differentially expressed alleles are enriched in the functions of auxin response and the starch synthesis pathway. The high heterozygosity of cassava 'Xinxuan 048' leads to rapid trait segregation in the first selfed generation. This study provides a theoretical basis and genomic resource for molecular breeding of cassava haploids., Competing Interests: The authors declare that they have no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background: EDIL3, which contains epidermal growth factor-like repeats and discoidin I-like domains, is a secretory protein that plays an important role in embryonic development and various illnesses. However, the biological function of EDIL3 in gastric cancer (GC) is still unclear. The objective of this research was to explore the role and potential mechanism of EDIL3 in GC., Methods: In this study, we used the GEPIA, HPA, MethSurv, SMART, STRING, GeneMANIA, LinkedOmics TIMER, TIMER2.0, TISIDB, and RNAactDrug databases to comprehensively analyze the roles of EDIL3 in GC. To validate the in silico findings, EDIL3 expression was measured in our collected GC tissues. Meanwhile, several in vitro experiments were performed to test the function of EDIL3 in GC., Results: We found that EDIL3 was highly expressed in GC and associated with adverse clinical features. In vitro assays revealed that EDIL3 promoted the proliferation, migration, and invasion of GC cells. The functions of EDIL3 and co-expression genes were significantly associated with extracellular structure organization and matrix receptor interaction. EDIL3 expression was positively associated with numerous tumor-infiltrating immune cells and their biomarkers., Conclusion: This study determined that EDIL3 may function as an oncogene and is associated with immune infiltration in GC. EDIL3 could be used as a potential therapeutic target for GC., Competing Interests: The authors declare there are no competing interests., (©2023 Ke et al.)

Due to the development of sequencing technology and the great reduction in sequencing costs, an increasing number of plant genomes have been assembled, and numerous genomes have revealed large amounts of variations. However, a single reference genome does not allow the exploration of species diversity, and therefore the concept of pan-genome was developed. A pan-genome is a collection of all sequences available for a species, including a large number of consensus sequences, large structural variations, and small variations including single nucleotide polymorphisms and insertions/deletions. A simple linear pan-genome does not allow these structural variations to be intuitively characterized, so graph-based pan-genomes have been developed. These pan-genomes store sequence and structural variation information in the form of nodes and paths to store and display species variation information in a more intuitive manner. The key role of graph-based pan-genomes is to expand the coordinate system of the linear reference genome to accommodate more regions of genetic diversity. Here, we review the origin and development of graph-based pan-genomes, explore their application in plant research, and further highlight the application of graph-based pan-genomes for future plant breeding., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Live attenuated vaccines (LAVs) replicate in the respiratory/oral mucosa, mimic natural infection, and can induce mucosal and systemic immune responses to the full repertoire of SARS-CoV-2 structural/nonstructural proteins. Generally, LAVs produce broader and more durable protection than current COVID-19 vaccines. We generated a temperature-sensitive (TS) SARS-CoV-2 mutant TS11 via cold-adaptation of the WA1 strain in Vero E6 cells. TS11 replicated at >4 Log10-higher titers at 32 °C than at 39 °C. TS11 has multiple mutations, including those in nsp3, a 12-amino acid-deletion spanning the furin cleavage site of the S protein and a 371-nucleotide-deletion spanning the ORF7b-ORF8 genes. We tested the pathogenicity and protective efficacy of TS11 against challenge with a heterologous virulent SARS-CoV-2 D614G strain 14B in Syrian hamsters. Hamsters were randomly assigned to mock immunization-challenge (Mock-C) and TS11 immunization-challenge (TS11-C) groups. Like the mock group, TS11-vaccinated hamsters did not show any clinical signs and continuously gained body weight. TS11 replicated well in the nasal cavity but poorly in the lungs and caused only mild lesions in the lungs. After challenge, hamsters in the Mock-C group lost weight. In contrast, the animals in the TS11-C group continued gaining weight. The virus titers in the nasal turbinates and lungs of the TS11-C group were significantly lower than those in the Mock-C group, confirming the protective effects of TS11 immunization of hamsters. Histopathological examination demonstrated that animals in the Mock-C group had severe pulmonary lesions and large amounts of viral antigens in the lungs post-challenge; however, the TS11-C group had minimal pathological changes and few viral antigen-positive cells. In summary, the TS11 mutant was attenuated and induced protection against disease after a heterologous SARS-CoV-2 challenge in Syrian hamsters.

Objectives: To evaluate the effectiveness of a pilot smoking cessation service in an emergency department (ED) clinical observation unit., Study Design: A descriptive case series review was undertaken of smoking cessation service patients in the short-stay unit of an acute hospital in Singapore from July 1, 2018, to December 31, 2019., Methods: Upon admission, ED nurses screen all patients regarding their current smoking status and implement the 5 A's framework, which involves the steps of Ask-Advise-Assess-Assist-Arrange. Patients in the "contemplation" and "preparation" stages were offered the following components: (1) a bedside counseling session by a pharmacist and (2) a follow-up appointment at an outpatient smoking cessation clinic. Postdischarge follow-up telephone calls at 1, 6, and 12 months were carried out as part of the study data collection to obtain abstinence information., Results: Forty-seven patients were included in the study; the majority were male (n = 41; 87.2%). The median numbers of cigarettes smoked per day at baseline, 1 month, 6 months, and 12 months were 14, 5, 3, and 5, respectively. The overall point-prevalence abstinence rates over the same follow-up time points were 26.5%, 38.7%, and 31.3%, respectively. The proportions of patients lost to follow-up at 1 month, 6 months, and 12 months were 27.7%, 34.0%, and 31.9%, respectively., Conclusions: Given the small sample and high number of uncontactable patients, more research is needed to assess whether the trend toward increasing point-prevalence abstinence rate over time and the trend toward decreasing median number of cigarettes smoked are observed in a larger sample.

Purpose: Developing the ideal drug or dressing is a serious challenge to controlling the occurrence of antibacterial infection during wound healing. Thus, it is important to prepare novel nanofibers for a wound dressing that can control bacterial infections. In our study, the novel self-assembled nanofibers of benzalkonium bromide with bioactive peptide materials of IKVAV and RGD were designed and fabricated., Methods: Different drug concentration effects of encapsulation efficacy, swelling ratio and strength were determined. Its release profile in simulated wound fluid and its cytotoxicity were studied in vitro. Importantly, the antibacterial efficacy, inhibition of biofilm formation effect and wound healing against MRSA infections in vitro and in vivo were performed after observing the tissue toxicity in vivo., Results: It was found that the optimized drug load (0.8%) was affected by the encapsulation efficacy, swelling ratio, and strength. In addition, the novel nanofibers with average diameter (222.0 nm) and stabile zeta potential (-11.2 mV) have good morphology and characteristics. It has a delayed released profile in the simulated wound fluid and good biocompatibility with L929 cells and most tissues. Importantly, the nanofibers were shown to improve antibacterial efficacy, inhibit biofilm formation, and lead to accelerated wound healing following infection with methicillin-resistant Staphylococcus aureus ., Conclusion: These data suggest that novel nanofibers could effectively shorten the wound-healing time by inhibiting biofilm formation, which make it promising candidates for treatment of MRSA-induced wound infections., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Ran et al.)

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 129 million confirm cases. Many health authorities around the world have implemented wastewater-based epidemiology as a rapid and complementary tool for the COVID-19 surveillance system and more recently for variants of concern emergence tracking. In this study, three SARS-CoV-2 target genes (N1 and N2 gene regions, and E gene) were quantified from wastewater influent samples (n = 250) obtained from the capital city and 7 other cities in various size in central Ohio from July 2020 to January 2021. To determine human-specific fecal strength in wastewater samples more accurately, two human fecal viruses (PMMoV and crAssphage) were quantified to normalize the SARS-CoV-2 gene concentrations in wastewater. To estimate the trend of new case numbers from SARS-CoV-2 gene levels, different statistical models were built and evaluated. From the longitudinal data, SARS-CoV-2 gene concentrations in wastewater strongly correlated with daily new confirmed COVID-19 cases (average Spearman's r = 0.70, p < 0.05), with the N2 gene region being the best predictor of the trend of confirmed cases. Moreover, average daily case numbers can help reduce the noise and variation from the clinical data. Among the models tested, the quadratic polynomial model performed best in correlating and predicting COVID-19 cases from the wastewater surveillance data, which can be used to track the effectiveness of vaccination in the later stage of the pandemic. Interestingly, neither of the normalization methods using PMMoV or crAssphage significantly enhanced the correlation with new case numbers, nor improved the estimation models. Viral sequencing showed that shifts in strain-defining variants of SARS-CoV-2 in wastewater samples matched those in clinical isolates from the same time periods. The findings from this study support that wastewater surveillance is effective in COVID-19 trend tracking and provide sentinel warning of variant emergence and transmission within various types of communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1 - , and 1 of 2 BCR-ABL1 + cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.

Heterozygous mutations in the BRCA1 gene predispose women to breast and ovarian cancer, while biallelic BRCA1 mutations are a cause of Fanconi anemia (FA), a rare genetic disorder characterized by developmental abnormalities, early-onset bone marrow failure, increased risk of cancers, and hypersensitivity to DNA-crosslinking agents. BRCA1 is critical for homologous recombination of DNA double-strand breaks (DSB). Through its coiled-coil domain, BRCA1 interacts with an essential partner, PALB2, recruiting BRCA2 and RAD51 to sites of DNA damage. Missense mutations within the coiled-coil domain of BRCA1 (e.g., L1407P) that affect the interaction with PALB2 have been reported in familial breast cancer. We hypothesized that if PALB2 regulates or mediates BRCA1 tumor suppressor function, ablation of the BRCA1-PALB2 interaction may also elicit genomic instability and tumor susceptibility. We generated mice defective for the Brca1-Palb2 interaction (Brca1 L1363P in mice) and established MEF cells from these mice. Brca1 L1363P/L1363P MEF exhibited hypersensitivity to DNA-damaging agents and failed to recruit Rad51 to DSB. Brca1 L1363P/L1363P mice were viable but exhibited various FA symptoms including growth retardation, hyperpigmentation, skeletal abnormalities, and male/female infertility. Furthermore, all Brca1 L1363P/L1363P mice exhibited macrocytosis and died due to bone marrow failure or lymphoblastic lymphoma/leukemia with activating Notch1 mutations. These phenotypes closely recapitulate clinical features observed in patients with FA. Collectively, this model effectively demonstrates the significance of the BRCA1-PALB2 interaction in genome integrity and provides an FA model to investigate hematopoietic stem cells for mechanisms underlying progressive failure of hematopoiesis and associated development of leukemia/lymphoma, and other FA phenotypes. SIGNIFICANCE: A new Brca1 mouse model for Fanconi anemia (FA) complementation group S provides a system in which to study phenotypes observed in human FA patients including bone marrow failure. See related commentary by Her and Bunting, p. 4044 ., (©2020 American Association for Cancer Research.)

The theory of " tian - yin - yang " of Zhuang medicine was explored and the academic achievements and experience of professor HUANG Jin - ming were summarized to explain the theory and clinical characteristics of tian - yin - yang acupuncture, an acupuncture school of Huang 's Zhuang medicine of Guangxi. This acupuncture method is guided by the theory of "three- qi synchronization" and " tian - yin - yang " of Zhuang medicine, based on the theory of "three channels and two paths", with regulating qi as the method and regulating spirit as the basis. After the patient is calmed and resting, the micro needle shallow needling technique is adopted, mainly at the umbilical ring point, so as to achieve the purpose of regulating the mind and treating the root cause.

Background : The aberrant activation of the Sonic hedgehog (Shh) signaling pathway is involved in progression of several types of cancer, including gastric cancer (GC). However, it remains uncertain whether it also plays a critical role in promoting cancer initiation and progression by inducing epithelial-to-mesenchymal transition (EMT) in GC. Thus, the aim of the present study was to determine whether the Shh pathway is involved in GC, and to investigate the function of the Shh pathway in the induction of EMT in GC. Materials and methods : The expression levels of Shh pathway members and EMT markers were examined in GC tissues by immunohistochemistry. The association between these factors and patient clinicopathological characteristics was analyzed. In addition, Gli-antagonist 61 (GANT61) was used to block Shh/Gli1 pathway activity, and recombinant Shh proteins (N-Shh) were used to activate the Shh pathway in GC cells. Wound healing and Transwell invasion and migration assays were performed to assess the effects of the Shh pathway on the migration and invasion of GC cells in vitro . Furthermore, western blot analysis was used to examine the changes in protein expression. Results : The results demonstrated that these Shh/Gli1 pathway members were upregulated in GC tissues, and that Gli1 upregulation was associated with tumor progression and a poor prognosis. Gli1 expression was negatively associated with E-cadherin (E-Cad) expression, and positively with Vimentin (VIM) expression in GC specimens. Further analysis revealed that when the Shh/Gli1 pathway was activated, the migratory and invasive abilities of GC cells were enhanced, and the expression levels of Gli1 and VIM were increased, while E-Cad expression was decreased. Opposite results were observed when the Shh/Gli1 pathway was blocked by GANT61. Conclusions : The present study indicated that the Shh/Gli1 pathway exhibits an abnormal activation pattern in GC with possible predictive and prognostic significance. The Shh/Gli1 pathway may promote the migratory and invasive potential of GC cells by inducing EMT. The Shh/Gli1 pathway can thus be considered as a potential therapeutic target for GC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

Introduction: Low body weight in Parkinson's disease (PD) is poorly understood despite the associated risks of malnutrition, fractures, and death. Sarcopenia (loss of muscle bulk and strength) and frailty are geriatric syndromes that are likewise associated with adverse health outcomes, yet have received scant attention in PD. We studied body composition, sarcopenia, frailty, and their clinico-biological correlates in PD., Methods: 93 patients and 78 spousal/sibling controls underwent comprehensive assessment of diet, clinical status, muscle strength/performance, frailty, body composition (using dual-energy X-ray absorptiometry), and serum levels of neurogastrointestinal hormones and inflammatory markers., Results: PD patients were older than controls (66.0 ± 8.5 vs. 62.4 ± 8.4years, P = 0.003). Mean body mass index (24.0 ± 0.4 vs. 25.6 ± 0.5kg/m2, P adjusted  = 0.016), fat mass index (7.4 ± 0.3 vs. 9.0 ± 0.3kg/m2, P adjusted <0.001), and whole-body fat percentage (30.7 ± 0.8 vs. 35.7 ± 0.9%, P adjusted <0.001) were lower in patients, even after controlling for age and gender. There were no between-group differences in skeletal muscle mass index and whole-body bone mineral density. Body composition parameters did not correlate with disease duration or motor severity. Reduced whole-body fat percentage was associated with higher risk of motor response complications as well as higher levels of insulin-growth factor-1 and inflammatory markers. PD patients had a higher prevalence of sarcopenia (17.2% vs. 10.3%, P adjusted  = 0.340) and frailty (69.4% vs. 24.2%, P adjusted  = 0.010). Older age and worse PD motor severity were predictors of frailty in PD., Conclusions: We found reduced body fat with relatively preserved skeletal muscle mass, and a high prevalence of frailty, in PD. Further studies are needed to understand the patho-mechanisms underlying these alterations., (Copyright © 2018. Published by Elsevier Ltd.)

Genistein is a kind of isoflavone compounds， also called phytoestrogens， with clinical effects on cardiovascular disease， cancer and postmenopausal-related gynecological diseases， and also has the potentiality in the prevention and treatment of Alzheimer's disease(AD). In this study， the protective effect of genistein on Aβ₂₅₋₃₅-induced PC12 cell injury and effect on CaM-CaMKIV signaling pathway were observed to investigate its mechanism for AD. PC12 cells were cultured in vitro and then the safe concentration of genistein and the modeling concentration and optimal time point of administration of Aβ₂₅₋₃₅ were screened by MTT assay. After being pretreated with different concentrations of genistein(25， 50， 100 μmol·L⁻¹) on PC12 cells， the AD model of PC12 cells was induced by Aβ₂₅₋₃₅. Then the survival rate of cells was detected by MTT assay; morphological change of cells was observed under the inverted microscope， and apoptosis of cells was assessed by AO/EB fluorescence staining; the neuroprotective effects of genistein on AD cell model were observed and the optimal concentration of genistein was determined. Expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were detected by qRT-PCR and Western blot assay， respectively. The results showed that as compared with the blank group， the cell survival rate was decreased; the cell damage and apoptosis were increased; and the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau were increased in AD model group. Genistein could significantly improve the cell survival rate， reduce the cell damage and apoptosis of AD cell model， and significantly down-regulate the expressions of mRNA and protein levels of CaM， CaMKK， CaMKIV and tau of AD cell model. These results indicated that genistein has obviously neuroprotective effect on the AD cell model induced by Aβ₂₅₋₃₅， and the mechanism may be related to the down-regulation of CaM-CaMKIV signaling pathway and Tau protein expression., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

It is widely accepted that keratinocytes act as non‑professional antigen‑presenting cells and support superantigen‑induced proliferation of resting T cells; however, it remains unknown whether keratinocytes function in situ with T cells via a non‑contact mechanism. The current study used a transwell co‑culture system and demonstrated, for the first time to the best of the authors' knowledge, that HaCaT cells (the human keratinocyte cell line) did induce T cell proliferation via indirect contact. The data further indicated that exosomes, small membrane vesicles that transfer antigens to recipient cells, are also involved in the superantigen‑associated immunity of keratinocytes. The current study provided experimental evidence that HaCaT‑exosomes contained MHC I and II, and could interact with T cells. In addition, following interferon γ stimulation, Staphylococcal aureus enterotoxin B‑loaded HaCaT cells secreted exosomes to induce the proliferation of CD4+ and CD8+ T cells in vitro. This novel biological function of exosomes reveals a new mechanism of how keratinocytes participate in bacterial superantigen‑induced immune responses.

We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052μM and 0.25±0.028μM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1. As in SUP-B15, givinostat induced apoptosis in both cell lines but showed different levels of cleavage of the procaspase proteins Casp-3, Casp-7 and PARP. Levels of cell cycle-DNA repair regulator p21, CHK1 and FANCD2 levels were markedly affected by givinostat treatment. These data further enrich our understanding of the mechanisms of the antineoplastic effects of givinostat in B-ALL and provide a preclinical rationale for the inclusion of givinostat or similar agent in leukemia therapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The membrane-bound transcription factors, SREBPs (sterol regulatory element-binding proteins), play a central role in regulating lipid metabolism. The transcriptional activation of SREBPs requires the key protein SCAP (SREBP-cleavage activating protein) to translocate their precursors from the endoplasmic reticulum to the Golgi for subsequent proteolytic activation, a process tightly regulated by a cholesterol-mediated negative feedback loop. Our previous work showed that the SCAP/SREBP-1 pathway is significantly upregulated in human glioblastoma (GBM), the most deadly brain cancer, and that glucose-mediated N -glycosylation of SCAP is a prerequisite step for SCAP/SREBP trafficking. More recently, we demonstrated that microRNA-29 (miR-29) mediates a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling to control lipid metabolism. We found that SREBP-1, functioning as a transcription factor, promotes the expression of the miR-29 family members, miR-29a, -29b and -29c. In turn, the miR-29 isoforms reversely repress the expression of SCAP and SREBP-1. Moreover, treatment with miR-29 mimics effectively suppressed GBM tumor growth by inhibiting SCAP/SREBP-1 and de novo lipid synthesis. These findings, recently published in Cell Reports , strongly suggest that delivery of miR-29 in vivo may be a promising approach to treat cancer and metabolic diseases by suppressing SCAP/SREBP-1-regulated lipid metabolism., Competing Interests: Conflicting interests The authors have declared that no conflict of interests exist.

Purpose: Elevated lipogenesis regulated by sterol regulatory element-binding protein-1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is a novel characteristic of glioblastoma (GBM). The aim of this study was to identify effective approaches to suppress GBM growth by inhibition of SREBP-1. As SREBP activation is negatively regulated by endoplasmic reticulum (ER) cholesterol, we sought to determine whether suppression of sterol O-acyltransferase (SOAT), a key enzyme converting ER cholesterol to cholesterol esters (CE) to store in lipid droplets (LDs), effectively suppressed SREBP-1 and blocked GBM growth., Experimental Design: The presence of LDs in glioma patient tumor tissues was analyzed using immunofluorescence, immunohistochemistry, and electronic microscopy. Western blotting and real-time PCR were performed to analyze protein levels and gene expression of GBM cells, respectively. Intracranial GBM xenografts were used to determine the effects of genetically silencing SOAT1 and SREBP-1 on tumor growth., Results: Our study unraveled that cholesterol esterification and LD formation are signature of GBM, and human patients with glioma possess elevated LDs that correlate with GBM progression and poor survival. We revealed that SOAT1 is highly expressed in GBM and functions as a key player in controlling the cholesterol esterification and storage in GBM. Targeting SOAT1 suppresses GBM growth and prolongs survival in xenograft models via inhibition of SREBP-1-regulated lipid synthesis., Conclusions: Cholesterol esterification and storage in LDs are novel characteristics of GBM, and inhibiting SOAT1 to block cholesterol esterification is a promising therapeutic strategy to treat GBM by suppressing SREBP-1. Clin Cancer Res; 22(21); 5337-48. ©2016 AACR., Competing Interests: The authors declare that there are no any conflicts of interest for this manuscript., (©2016 American Association for Cancer Research.)

Dysregulated lipid metabolism is a characteristic of malignancies. Sterol regulatory element binding protein 1 (SREBP-1), a transcription factor playing a central role in lipid metabolism, is highly activated in malignancies. Here, we unraveled a link between miR-29 and the SCAP (SREBP cleavage-activating protein)/SREBP-1 pathway in glioblastoma (GBM) growth. Epidermal growth factor receptor (EGFR) signaling enhances miR-29 expression in GBM cells via upregulation of SCAP/SREBP-1, and SREBP-1 activates miR-29 expression via binding to specific sites in its promoter. In turn, miR-29 inhibits SCAP and SREBP-1 expression by interacting with their 3' UTRs. miR-29 transfection suppressed lipid synthesis and GBM cell growth, which were rescued by the addition of fatty acids or N-terminal SREBP-1 expression. Xenograft studies showed that miR-29 mimics significantly inhibit GBM growth and prolong the survival of GBM-bearing mice. Our study reveals a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling mediated by miR-29 and suggests that miR-29 treatment may represent an effective means to target GBM., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Tumorigenesis is associated with increased glucose consumption and lipogenesis, but how these pathways are interlinked is unclear. Here, we delineate a pathway in which EGFR signaling, by increasing glucose uptake, promotes N-glycosylation of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) and consequent activation of SREBP-1, an ER-bound transcription factor with central roles in lipid metabolism. Glycosylation stabilizes SCAP and reduces its association with Insig-1, allowing movement of SCAP/SREBP to the Golgi and consequent proteolytic activation of SREBP. Xenograft studies reveal that blocking SCAP N-glycosylation ameliorates EGFRvIII-driven glioblastoma growth. Thus, SCAP acts as key glucose-responsive protein linking oncogenic signaling and fuel availability to SREBP-dependent lipogenesis. Targeting SCAP N-glycosylation may provide a promising means of treating malignancies and metabolic diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To elucidate the clinical significance of the methylated status of CpG site count of PCDH10 promoter in the survival prediction in gastric cancer (GC)., Methods: In the previous study, we demonstrated that the methylated CpG site count was significantly associated with the overall survival (OS) of GC patients by using the bisulfite genomic sequencing (BGS) with no less than five clones per sample. It was so complex and expensive for patients to undergo the BGS clones. In this study, we detected the different CpG site counts (hypermethylated and hypomethylated) of PCDH10 DNA promoter in GC samples of 471 patients by directly bisulfite genomic sequencing (D-BGS) without any clone. Furthermore, we evaluated the relationships between the methylated status of PCDH10 promoter and OS., Results: Two hundred and fifty-seven of 471 (54.6%) GC patients were identified to present with PCDH10 promoter methylation by D-BGS. Patients who presented with 5 or more methylated CpG site counts of PCDH10 promoter had significantly poorer prognosis than patients who with less than 5 methylated CpG site counts of PCDH10 promoter (p= 0.039). With the multivariate survival analysis, we demonstrated that T stage, N stage and the hypermethylated CpG site counts of PCDH10 DNA promoter were the independent predictors of OS of GC patients. In addition, the hypermethylated CpG site counts of PCDH10 DNA promoter had smaller Akaike information criterion (AIC) and Bayesian information criterion (BIC) values than the other two independent predictors of the OS, indicating the hypermethylated CpG site counts of PCDH10 DNA promoter as the best prognostic predictor of GC., Conclusions: Our present findings suggested that the hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the prognosis of GC was reasonable by using the D-BGS.

Aim: To investigate the impact of prognostic nutritional index (PNI) on the postoperative complications and long-term outcomes in gastric cancer patients undergoing total gastrectomy., Methods: The data for 386 patients with gastric cancer were extracted and analyzed between January 2003 and December 2008 in our center. The patients were divided into two groups according to the cutoff value of the PNI: those with a PNI ≥ 46 and those with a PNI < 46. Clinicopathological features were compared between the two groups and potential prognostic factors were analyzed. The relationship between postoperative complications and PNI was analyzed by logistic regression. The univariate and multivariate hazard ratios were calculated using the Cox proportional hazard model., Results: The optimal cutoff value of the PNI was set at 46, and patients with a PNI ≥ 46 and those with a PNI < 46 were classified into PNI-high and PNI-low groups, respectively. Patients in the PNI-low group were more likely to have advanced tumor (T), node (N), and TNM stages than patients in the PNI-high group. The low PNI is an independent risk factor for the incidence of postoperative complications (OR = 2.223). The 5-year overall survival (OS) rates were 54.1% and 21.1% for patients with a PNI ≥ 46 and those with a PNI < 46, respectively. The OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stages II (P = 0.001) and III (P < 0.001) disease., Conclusion: The PNI is a simple and useful marker not only to identify patients at increased risk for postoperative complications, but also to predict long-term survival after total gastrectomy. The PNI should be included in the routine assessment of advanced gastric cancer patients.

Behcet's disease (BD) accompanied by intestinal involvement is called intestinal BD. Although recent studies have attained positive feedback with the administration of anti-TNF-α agents in patients with BD, only a few reports on the study of etanercept in intestinal BD have been found. In this study, 35 cases of intestinal BD were treated with conventional therapy (prednisone or methotrexate) for a minimum period of 3 months (group 1). Another 19 patients who failed to respond to conventional therapy were then treated with etanercept (25 mg twice a week for 3 months). During each subsequent relapse, the patients were given the same treatment. The main outcome measures were the four criteria for diagnosis of BD (buccal ulcers, genital ulcers, ocular lesions, and skin lesions), the manifestation of intestinal involvement (abdominal symptoms, double-balloon enteroscopy), laboratory examinations of the acute phase reactants (erythrocyte sedimentation rate) and C-reactive protein, and relapses. As a result of the administered therapy, the healing rate of buccal and genital ulcers, the remission rate of ocular lesions, skin lesions, and abdominal symptoms, the healing rate of intestinal ulcers, and the recovery rate of ESR and CRP were significantly higher in group 2 than those of group 1. The relapse rate in the etanercept therapy was reduced significantly when compared with conventional therapy group. In conclusion, etanercept treatment, in contrast to the conventional therapy, can result in better curative effect and less adverse reactions in intestinal BD.

Objective: The aim of this study was to investigate the prognostic value of metastatic lymph node ratio (LNR) in patients having radical resection for stage III gastric cancer., Methods: A total of 365 patients with stage III gastric cancer who underwent radical resection between 2002 and 2008 at Tianjin Medical University Cancer Institute and Hospital were analyzed. The cut-point survival analysis was adopted to determine the appropriate cutoffs for LNR. Kaplan-Meier survival curves and log-rank tests were used for the survival analysis., Results: By cut-point survival analysis, the LNR staging system was generated using 0.25 and 0.50 as the cutoff values. Pearson's correlation test revealed that the LNR was related with metastatic lymph nodes but not related with total harvested lymph nodes. Cox regression analysis showed that depth of invasion and LNR were the independent predictors of survival (p<0.05). There was a significant difference in survival between each pN stages classified by the LNR staging, however no significant difference was found in survival rate between each LNR stages classified by the pN staging., Conclusions: The LNR is an independent prognostic factor for survival in stage III gastric cancer and is superior to the pN category in TNM staging. It may be considered as a prognostic variable in future staging system.

Aim: To elucidate the potential impact of examined lymph nodes (eLNs) on long-term survival of node-negative gastric cancer patients after curative surgery., Methods: A total of 497 node-negative gastric cancer patients who underwent curative gastrectomy between January 2000 and December 2008 in our center were enrolled in this study. Patients were divided into 4 groups according to eLNs through cut-point analysis. Clinicopathological features were compared between ≤ 15 eLNs group and > 15 eLNs group and potential prognostic factors were analyzed. The Log-rank test was used to assess statistical differences between the groups. Independent prognostic factors were identified using the Cox proportional hazards regression model. Stratified analysis was performed to investigate the impact of eLNs on patient survival in each stage. Overall survival was also compared among the four groups. Finally, we explored the recurrent sites associated with eLNs., Results: Patients with eLNs > 15 had a better survival compared with those with eLNs ≤ 15 for the entire cohort. By the multivariate survival analysis, we found that the depth of invasion and the number of eLNs were the independent predictors of overall survival (OS) of patients with node-negative gastric cancer. According to the cut-point analysis, T2-T4 patients with 11-15 eLNs had a significantly longer mean OS than those with 4-10 eLNs or 1-3 eLNs. Patients with ≤ 15 eLNs were more likely to experience locoregional and peritoneal recurrence than those with > 15 eLNs., Conclusion: Number of eLNs could predict the prognosis of node-negative gastric cancer, and dissection of > 15 eLNs is recommended during lymphadenectomy so as to improve the long-term survival.

Objective: To compare post-operative long-term complications and quality of life of two digestive reconstruction procedures after total gastrectomy., Methods: A total of 109 gastric cancer patients in Tianjin Medical University Cancer Hospital from March 2012 to February 2013 were prospectively enrolled and randomly divided into functional jejunal interposition (FJI) group (52 cases) and Roux-en-Y (R-Y) group (57 cases). The post-operative complications, nutritional status, and the quality of life were compared between two groups., Results: One, 3 and 6 months after operation, the incidence of R-S syndrome in FJI group was lower as compared to R-Y group[13% (6/45) vs. 37% (18/49), 3% (1/30) vs. 42% (14/33), 5% (1/21) vs. 48% (11/23), all P<0.01], while 3 months after operation, the incidence of reflux and heartburn in FJI group was higher[53% (16/30) vs. 21% (7/33), P<0.01; 37% (11/30) vs. 12% (4/33), P<0.05]. There were no significant differences in quality of life questionnaire QLQ-C30 between R-Y and FJI groups. QLQ-STO22 stomach module revealed in FJI group, the eating score was better, but reflux score was worse as compared to R-Y group 3 months after operation (all P<0.01)., Conclusions: Functional jejunal interposition keeps intestinal continuity preserving and food duodenal passing, which is a reasonable digestive reconstruction procedure.

Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

Recently, stathmin 1 has been proposed to function as an oncogene based on some relevant studies in multiple types of human cancers. However, the role of stathmin 1 in gastric cancer carcinogenesis has not been elucidated yet. The aim of this study was to investigate the expression of stathmin 1 as well as its association with overall survival of gastric cancer patients. The expression of stathmin 1 was detected by real-time quantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, stathmin 1 expression was analyzed by immunohistochemistry in paraffin samples from 210 primary gastric cancer patients. The expression levels of stathmin 1 mRNA and protein in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of stathmin 1 is correlated with Lauren's classification, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (all P < 0.05). Univariate analysis showed that high stathmin 1 expression was associated with poor prognosis in gastric cancer patients (P = 0.040). Multivariate analysis demonstrated that only lymph node metastasis and TNM stage were the independent prognostic indicators for gastric cancer. Stathmin 1 expression status is not an independent prognostic factor for patients with gastric cancer. Further subgroup analysis revealed that stathmin 1 expression was significantly correlated with prognosis in diffuse type gastric cancer. This research showed that the stathmin 1 overexpression might play an important role in the pathogenesis and subsequent progression of gastric cancer. Stathmin 1 could also be a potential therapeutic target in gastric cancer, especially for diffuse type gastric cancer.

Aim: To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis., Methods: Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected, from January 2002 to December 2006, were analyzed retrospectively. Patients with pT4 stage or distant metastasis were excluded. We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features, such as age, tumor size, tumor location and depth of invasion. At the same time, the relationship between postoperative chemotherapy and the 5-year survival rate among different subgroups were also analyzed., Results: The overall 5-year survival rate of the entire cohort was 63.7%. The 5-year survival rate was poor in those patients who were: (1) more than 65 years old; (2) with tumor size larger than 4 cm; (3) with tumor located in the upper portion of the stomach; and (4) with pT3 tumor. The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor (P = 0.019), but not in other subgroups. Moreover, there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups (P > 0.05)., Conclusion: For gastric cancer patients without lymph node metastasis, extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor. However, there was no evidence of a survival benefit from postoperative chemotherapy alone.

Objective: To investigate the clinicopathological characteristics and prognostic factors of patients with pathological stage pN3 gastric cancer., Methods: A retrospective study of 310 patients with histologically confirmed pN3 stage gastric cancer undergoing radical gastrectomy from January 2000 to December 2006 in our department was performed. The Kaplan-Meier method was used to analyze the survival. Log-rank test and Cox regression model were carried out for univariate and multivariate analyses., Results: All the patients were followed up for 2 to 103 (mean 35.7) months. The overall 5-year survival rate was 14.6%. There were 201 cases with stage pN3a and 109 cases with stage pN3b, and the 5-year survival rates were 16.8% and 10.3% respectively (P=0.013). Univariate analysis showed that tumor location, Borrmann type, depth of tumor invasion, surgical method, metastatic lymph node ratio, and pN stage were associated with postoperative survival (all P<0.05). The multivariate analysis revealed that depth of tumor invasion, surgical method and metastatic lymph node ratio were independent prognostic factors, while the pN stage was not. The difference of 5-year survival rate between pN3a and pN3b subgroups was significant in pT4a patients (16.1% vs. 12.8%, P=0.001), while such difference was not significant in pT4b patients (8.6% vs. 3.1%, P=0.137)., Conclusions: Prognosis of patients with pN3 stage gastric cancer after radical resection is poor. Depth of tumor invasion and surgical method are independent prognostic factors for pN3 stage gastric cancer. Metastatic lymph node ratio is valuable to predict the prognosis of pN3 stage patients. The pN3 staging of the 7th UICC provides a more accurate prediction of prognosis.

Objective: To investigate the clinicopathological characteristics and prognostic factors of bone metastasis in gastric cancer patients., Methods: Clinicopathological data of 66 gastric cancer patients with bone metastasis, who were treated at the Tianjin Medical University Cancer Institute and Hospital from October 1997 to September 2011, were analyzed retrospectively. The clinicopathological characteristics of the primary cancer and bone metastasis were summarized and the prognosis was analyzed., Results: Of 66 patients, 4 underwent operation, 28 chemotherapy, 32 inhibitors of bone resorption,8 local treatment and 23 symptomatic treatment alone. The median survival time of these 66 patients was 5 months (95%CI:3.3-6.7 months). The 1-, 2- and 3-year survival rates were 9.1%, 3.0% and 1.5%, respectively. Univariate Log-rank test indicated that gender, bone metastasis combined with other distant metastasis and chemotherapy were significant prognostic factors (all P<0.05). Multivariate analysis revealed bone metastasis combined with other distant metastasis was an independent prognostic factor (P=0.011, RR=2.067, 95%CI:1.178-3.626)., Conclusions: Prognosis of patients with bone metastasis from gastric cancer is poor. Chemotherapy-based comprehensive treatment may improve the prognosis of these patients.

Objective: To explore the prognostic factors and to compare chemotherapy alone versus surgical resection plus chemotherapy for early stage primary gastric diffuse large B-cell lymphomas (DLBCL)., Methods: Clinical data of 75 patients who were diagnosed as primary gastric DLBCL between January 1993 and August 2008 in Cancer Institute and Hospital of Tianjin Medical University were reviewed retrospectively., Results: Among these 75 patients, 20 patients received chemotherapy alone and 55 underwent surgical resection plus chemotherapy. Complete remission rates were 65.0% (13/20) and 83.6% (46/55), effective rates were 75.0% (15/20) and 92.7% (51/55), and 5-year survival rates were 86.9% and 78.7% respectively in chemotherapy alone group and resection plus chemotherapy group, while the differences were not statistically significant (all P>0.05). Multivariate Cox regression model showed that international prognosis index (IPI) was the only independent prognostic factor (P<0.05, HR=11.350, 95%CI:1.011-127.371)., Conclusions: In early stage of DLBCL, IPI is the only independent prognostic factor. The clinical outcomes are comparable between chemotherapy alone and surgical resection plus chemotherapy.

To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA) at the auricular concha region (ACR) of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS), and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity.

Background: The 7th TNM staging is the first authoritative standard for evaluation of effectiveness of treatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed. In particular, the N3 sub-stage is becoming more conspicuous., Methods: Clinical data of 302 pN3M0 stage gastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital from January 2001 to May 2006 were retrospectively analyzed., Results: Location of tumor, depth of invasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate of lymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastric cancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis than other sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0. T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. In multivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors., Conclusions: The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should therefore be applied in the TNM stage system.

Background: Depressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response.This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention., Design: One hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period., Discussion: This study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical trials of acupuncture treatment., Trials Registration: Clinical Trials. ChiCTR-TRC-11001201 http://www.chictr.org/cn/

Objective: To evaluate the predicators of survival and recurrence after curative resection for gastric cancer patients with serosal invasion., Methods: Clinical and follow-up data of 280 patients with T4a gastric cancer(according to the 7th UICC TNM Classification for gastric cancer) who underwent curative resection for gastric cancer between January 1997 and December 2003 were analyzed retrospectively., Results: Five-year survival rate of these 280 patients was 50.0% and 158 patients (56.4%) presented with recurrence after surgery. The 3-year disease-free survival rate was 57.5%. The number of lymph node metastasis and metastatic lymph node ratio(MLR) were identified as the independent predicators for overall survival(P<0.05). The extent of lymph node metastasis was identified as the independent predicators for disease free survival (P<0.05). The extent of lymph node metastasis, the number of lymph node metastasis, and MLR were identified as the independent predicators for recurrence after surgery(P<0.05)., Conclusions: The number of lymph node metastases, extent of lymph node metastasis and MLR are independent predictors of overall survival and recurrence in T4a gastric cancer patients after curative resection.

Prostate cancer remains the second leading cause of cancer deaths among American men. Early diagnosis increases survival rate in patients; however, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment are necessary for inhibiting prostate cancer disease progression. Here, we have shown that miRNA-29b (miR-29b) expression was lower in prostate cancer cells (PC3 and LNCaP) as compared with immortalized prostate epithelial cells. Between these two prostate cancer cell lines, metastatic prostate cancer PC3 cells displayed lower expression of miR-29b. We also observed a significant downregulation of miR-29b expression in human prostate cancer tissues as compared with patient-matched nontumor tissues. PC3 cells ectopically expressing miR-29b inhibited wound healing, invasiveness, and failed to colonize in the lungs and liver of severe combined immunodeficient mice after intravenous injection, while PC3 cells expressing a control miRNA displayed metastasis. Epithelial cell marker E-cadherin expression was enhanced miR-29b transfected in prostate cancer cells as compared with cells expressing control miRNA. On the other hand, N-cadherin, Twist, and Snail expression was downregulated in PC3 cells expressing miR-29b. Together these results suggested that miR-29b acts as an antimetastatic miRNA for prostate cancer cells at multiple steps in a metastatic cascade. Therefore, miR-29b could be a potentially new attractive target for therapeutic intervention in prostate cancer., (©2012 AACR)

Unlabelled: OBJECTIVE To observe the effect of electroacupuncture (EA) stimulation of auricular concha region (ACR) on behavior changes of depression rats., Methods: A total of 80 male Wistar rats were randomized into depression model (model, n = 6), EA-ACR (n = 12), preventive EA-ACR (Pre-EA-ACR, n = 11) and EA-ear-tip (n = 12) groups. Depression model was established by chronic unpredictable mild stress for 21 days and isolated breeding. Open-field test and sucrose solution intake preference test were conducted to assess changes of the rats' behavior activities before modeling and on day 22, 36 and 50 after starting model. For rats of the pre-EA-ACR group, EA (2 Hz, 1 mA) was applied to the bilateral auricular concha area for 20 min, once daily for 14 days, beginning from the 8th day on after starting model preparation till the end of the modeling, and for rats of the EA-ACR and EA-ear-tip groups, EA was given to the bilateral ACR and ear-tips respectively, beginning after modeling, once daily for 14 days., Results: In comparison with pre-modeling, the percentages of sucrose solution consumption in rats of the model group decreased gradually from day 22 to 50 (P > 0.05). Compared with the model group,the percentage of sucrose solution consumption in the EA-ACR group was increased significantly on day 50 (P < 0.05), suggesting an inhibitory effect of EA on the reduction of sucrose intake preference at this time-point. No significant differences were found between the pre-EA-ACR and the model groups and between the EA-ear-tip and model groups as well as between the EA-ACR and model groups at most time-points (P > 0.05). Open-field test showed that in comparison with pre-modeling in the same one group, the total scores, crossing and rearing scores on day 22 were decreased considerably in the model and EA-ear-tip groups (P < 0.05, P < 0.01), rather than in the pre-EA-ACR and EA-ARC groups (P > 0.05), suggesting a suppressing effect of pre-EA-ACR and EA-ACR on depression behavior. Compared to day 22 in the same one group, the total scores, crossing and rearing scores on day 36 and 50 in the pre-EA-ACR and EA-ear-tip groups were decreased significantly (P < 0.05, P < 0.01)., Conclusion: EA of auricular concha region can restrain the development of depression behavioral status in depression rats, which is superior to that of EA of ear-tip.

Objective: To explore the risk factors for early recurrence (recurrence within 2 years) of proximal gastric cancer after radical resection., Methods: The clinical data of 367 proximal gastric cancer patients who underwent radical resection in the Cancer Institute and Hospital of Tianjin Medical University between January 2000 and May 2006 were reviewed. Among them, there are 71 patients (19.3%) with early recurrence. Univariate analysis and multivariate analysis were applied to investigate risk factors for early recurrence., Results: Univariate analysis showed that Borrmann type (P<0.01), histology type (P<0.01), depth of invasion (P<0.05), negative lymph nodes count (P<0.05) were risk factors for early recurrence of proximal gastric. On multivariate analysis, histology type (P<0.05), depth of invasion (P<0.05), negative lymph nodes counts (P<0.05) were independent risk factors for early recurrence of proximal gastric cancer. Negative lymph nodes in early recurrence patients were 8.4 ± 7.2, which were significantly less as compared to patients without early recurrence (10.7 ± 8.7) (P<0.05)., Conclusion: For T3 proximal gastric adenosquamous cancer, extended resection and lymphadenectomy should be considered. Intraoperative or postoperative adjuvant treatment should be administered as routine.

Objective: To explore the clinicopathological characteristics and prognostic factors of primary gastric lymphoma (PGL)., Methods: The clinical data of 204 patients with PGL was reviewed and analyzed. There were 106 males and 98 females, their age were 19 to 85 years (average age was 53.7 years). The Focal areas included gastric fundus lesions 41 cases (20.1%), stomach body lesions 127 cases (62.3%), distal gastric lesions 105 cases (51.5%), cardia lesions 13 cases (6.4%), duodenal bulb lesion 1 cases (0.5%). The clinical characteristics and the outcomes in patients with influence were analysed., Results: In 204 PGL patients, the most common complaints were abdominal pain (62.3%) and weight loss (52.9%). Most of the PGL patients appeared ulcerative (76.0%) and results showed that 62.7% patients involved single location. As to the factors of cellulate grading and pathological characteristics, most patients (87.7%) show low-grade or intermediate-grade lymphoma, Musshoff stages I and II (74.0%). In 186 patients with complete follow-up data, survival rates of 1-, 3- and 5-year were 75.8%, 63.4% and 60.2% respectively. The median overall survival time was 50.0 months. In univariate survival analysis, age (χ(2) = 5.030), level of LDH (χ(2) = 40.084), cellulate grading (χ(2) = 35.238), Musshoff stage (χ(2) = 71.601), tumor diameter (χ(2) = 12.018) and option of managements (χ(2) = 14.140) were obviously correlated with the prognosis (all P < 0.05). Musshoff stage (RR = 2.230, 95%CI: 1.372 - 3.625) and cellulate grading (RR = 1.892, 95%CI: 1.010 - 3.543) were independent prognostic factors in multivariable analysis (both P < 0.05). There was no prognostic difference between surgery and chemotherapy in stage I and II (χ(2) = 1.223, P = 0.542)., Conclusions: Musshoff stage and grade malignancy are independent prognostic factors. For patients with stage I and II, surgical resection is not the first-choice for clinical therapy.

Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle and modulate cyclin D1, cyclin E, and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression and induced PARP cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high-grade prostatic intraepithelial neoplasia in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed approximately 51% reduction of proliferating cell nuclear antigen expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell-cycle progression and proliferation., (2011 AACR)

Chronic stress often results in neurochemical changes in the central nervous system and may lead to the onset of depression. These neurochemical changes refer to alterations of activities of neurotransmitters, neuromediators, hormones and neuronal plasticity, etc. The underlying mechanism of acupuncture in the antidepressant effect is related to its regulatory effect on the neurochemical imbalance. In the present review, the authors summarize the progress of experimental researches on acupuncture treatment of depression from (1) monoamines neurotransmitters and their receptors, (2) gamma-aminobutyric acid and glutamate, (3) neuropeptide Y, (4) hypothalamus-pituitary-adrenal axis and hypothalamus-pituitary-throid axis activities, and (5) brain-derived neurotrophic factor. In addition, the authors also make an evaluation on the insufficiency of current studies and put forwards some suggestions on the future study.

Breast cancer is one of the most common cancers among women in the United States. Although there are effective drugs, such as cisplatin, for treating advanced cancers, many patients eventually develop resistance. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. In this study, the authors observed a significant upregulation of miR-203 expression in human breast cancer tissues as compared to patient-matched nontumor breast tissues. Knockdown of miR-203 following cisplatin treatment enhances p53, p21, and Bax protein expression. Furthermore, knockdown of miR-203 sensitized human breast cancer MCF-7 cells to cisplatin-mediated apoptotic cell death, as evident from caspase-9 and caspase-7 activation, and poly(ADP-ribose) polymerase (PARP) cleavage. Moreover, the authors have demonstrated that suppressor of cytokine signaling 3 (SOCS3) is a novel target of miR-203, and cisplatin treatment in miR-203 knockdown MCF-7 cells enhanced SOCS3 expression. Exogenous expression of SOCS3 in MCF-7 cells increased sensitization to cisplatin-mediated apoptosis. Together, the results suggested a novel role of miR-203 in conferring cisplatin resistance through suppression of SOCS3, implicating an additional therapeutic strategy may be helpful to overcome cisplatin resistance for breast cancer patients.

Objective: To evaluate the clinical efficacy of uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer., Methods: Clinical data of 419 patients who underwent distal gastrectomy for gastric cancer with complete follow-up data between March 2005 and March 2008 in the Cancer Institute and Hospital of Tianjin Medical University. Patients were divided into B I (138 cases with Billroth I reconstruction), M-B II (108 cases with modified Billroth II reconstruction), RY (46 cases with Roux-en-Y reconstruction) and Uncut RY (127 cases with uncut Roux-en-Y reconstruction) according to reconstructive methods., Results: Patients in the Uncut RY group had a larger tumor diameter, more T3, and poorer stage of disease compared to those in the B I (P<0.05). In Uncut RY group, the operative time and postoperative hospital stay were(132.6±19.2) minutes and (10.4±1.2) days respectively, shorter than those in RY group (142.5±11.7) minutes and (12.1±3.7) days(both P<0.05), alkaline reflex gastritis rate was 3.2%, lower than that in B I group (24.6%, P<0.05) and M-B II group (25.9%, P<0.05). Marginal ulcer rate in uncut RY group was lower compared to M-B II group (P=0.019), and incidence of Roux-en-Y stasis syndrome was less compared to RY group (P=0.000)., Conclusions: The uncut Roux-en-Y reconstruction is both feasible and safe. It can prevent alkaline reflex gastritis and Roux-en-Y stasis syndrome. It may be the preferred technique for reconstruction after distal gastrectomy.

Objective: To investigate the risk factors for the prognosis in patients with node-negative gastric cancer., Methods: Clinicopathological characteristics of 138 patients with node-negative gastric carcinoma undergoing curative gastrectomy from January 2000 to December 2005 were retrospectively analyzed., Results: The overall 5-year survival rate was 62.4%. The univariate analysis revealed that tumor size, tumor location, cell differentiation, invasive depth, operative type and Lauren histologic type had significant effects on the survival. The independent prognostic factors of these patients were tumor size, cell differentiation, and serosal involvement in multivariate analyses., Conclusion: For node-negative gastric cancer patients, tumor size, poor differentiation and serosal involvement are important markers to evaluate prognosis.