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Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-54/coif). The authors have no conflicts of interest to declare.

Objective: The non-invasive detection of Helicobacter pylori (H. pylori) and its resistance to clarithromycin and levofloxacin significantly improves the management of infected patients by enabling tailored eradication treatments without the need for endoscopic procedures. This study aimed to assess the effectiveness of real-time PCR (RT-PCR) assays in identifying H. pylori infection and antibiotic resistance in stool and gastric biopsy specimens., Patients and Methods: Stool and gastric biopsy samples were collected from patients within three days of post-hospitalization. A total of 115 samples were analyzed for H. pylori infection, and an additional 115 samples were evaluated for resistance to clarithromycin and levofloxacin using an RT-PCR-based molecular test. Statistical analyses were performed using (SPSS 26.0 IBM Corp., Armonk, NY, USA)., Results: Among 115 patients (53 males, average age 50.8±13.2 years), H. pylori was detected in 93.1% of stool samples and 93.9% of gastric biopsies. The RT-PCR assay demonstrated a sensitivity of 99.1% and a specificity of 100%, with an overall diagnostic accuracy of 99.1%. Clarithromycin resistance was found in 37.3% of stool and 46.9% of gastric biopsy specimens, with the assay showing 79.6% sensitivity and 98.4% specificity. Levofloxacin resistance was identified in 32.1% of stool samples and 31.3% of gastric biopsies, with 86.3% sensitivity and 91.1% specificity of the molecular test., Conclusions: The RT-PCR-based detection of H. pylori and its resistance to clarithromycin and levofloxacin in stool samples represents a promising approach to enhance eradication therapy outcomes, potentially improving treatment efficacy. Chictr.org.cn: ChiCTR2300070267.

Aspergillus versicolor , an endophytic fungus associated with the herbal medicine Pedicularis sylvatica , produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O -methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo 2 (AcO) 4 -induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC 50 value of 25.57 μM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP + )-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

Purpose: Pancreatic cancer (PC) is one of the most deadly human malignancies. Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against PC, but the mechanism remains incompletely elucidated. This study aimed to investigate the effects and mechanisms of curcumin on the invasion and migration of PC cells., Methods: Effect of curcumin on tissue factor pathway inhibitor (TFPI)-2 mRNA expression in PC cells was initially identified using qRT-PCR. Cytotoxicity of curcumin was assessed with MTT assays and IC50 was calculated. Involvement of ERK and JNK pathways, as well as protein expression of TFPI-2 and epithelial-mesenchymal transition (EMT)-related markers, were detected using immunoblotting. Invasion and migration of PC cells were examined using Transwell assays. TFPI-2 expression was manipulated by transfection with siRNA and shRNA. Rescue assays were used to validate the effect of curcumin on cell invasion and migration via TFPI-2., Results: Curcumin increased the expression of TFPI-2 mRNA and protein in PC cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in PC cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in PC cells., Conclusion: Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Nigrograna sp. LY66, an endophytic fungus associated with the herbal medicinal plant Clematis shensiensis, produced four undescribed steroids, nigergostanes A-D (1-4), including an unusual ketal-containing nigergostane (1), and four undescribed sesquiterpenoids decorated with cyclohexanone motifs, nigbisabolanes A-D (7-10), along with three known compounds, 23R-hydroxy-(20Z,24R)-ergosta-4,6,8(14),20(22)-tetraen-3-one (5), ergosta-5,7,22-trien-3β-ol (6), and curculonone A (11). The structures and absolute configurations of these undescribed compounds were confirmed using spectroscopic data (NMR and HRESIMS), modified Mosher's method, and ECD experiments. Additionally, compounds 5 and 8 displayed significant inhibition of nitric oxide generation in lipopolysaccharide-induced BV-2 microglial cells with IC 50 values of 2.8 and 2.7 μM, respectively, and is thus more potent than that of the positive control, quercetin (IC 50  = 8.77 μM). A molecular docking study revealed that 23-OH of 5 binds to the Y347 residue of inducible nitric oxide synthase (iNOS), whereas the 2-OH and 9,10-diol moieties of 8 bind to R381 and W463 and haeme residues of iNOS, respectively, which has rarely been reported in previous studies. These findings provide a set of undescribed lead compounds that can be developed into anti-neuroinflammatory agents., 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 © 2023 Elsevier Ltd. All rights reserved.)

Pancreatic cancer (PC) is a deadly disease, and its post-transcriptional gene regulation mechanism remains unclear. The abundant extracellular matrix (ECM) in PC plays an important role in tumor progression. This study is the first to focus on the role of N 6 -methyladenosine (m 6 A) RNA methylation, an emerging post-transcriptional regulatory mechanism, in the regulation of the ECM in PC. Here, we found that ADAMTS2, COL12A1, and THBS2 were associated with the prognosis of PC by comprehensive analysis of differentially expressed genes from two independent GEO expression profile datasets and m 6 A-related genes in RMVar database (PAAD). GO and KEGG enrichment analysis found that these m 6 A-related targets are chiefly functionally concentrated in the ECM region and participate in ECM signal transduction. Correlation analysis revealed that these genes can be regulated by the demethylase FTO. Cell biology function assays showed that knockdown of FTO-inhibited PC cell abilities to migrate and invade in vitro. qRT-PCR and MeRIP experiments showed that after knockdown of FTO, the mRNA levels of ADAMTS2, COL12A1, and THBS2 and their m 6 A modification levels were significantly reduced. These results indicate that m 6 A RNA demethylation is associated with the regulation of ECM in PC. In conclusion, m 6 A RNA demethylase FTO regulates ECM-related genes and promotes PC cell abilities to migrate and invade, our work provides a new perspective on the molecular mechanism of PC progression., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Pancreatic cancer (PC) is one of the most fatal cancers with a very poor prognosis. Here, we found that N 6 -methyladenosine (m 6 A) RNA demethylase fat mass and obesity-related protein (FTO) promote the growth, migration and invasion of PC. FTO expression level is increased in human PC and is associated with poor prognosis of PC patients. Knockdown of FTO increases m 6 A methylation of TFPI-2 mRNA in PC cells, thereby increasing mRNA stability via the m 6 A reader YTHDF1, resulting in up-regulation of TFPI-2 expression, and inhibits PC proliferation, colony formation, sphere formation, migration and invasion in vitro , as well as tumour growth in vivo . Rescue assay further confirms that FTO facilitates cancer progression by reducing the expression of TFPI-2. Mechanistically, FTO promotes the progression of PC at least partially through reducing m 6 A/YTHDF1 mediated TFPI-2 mRNA stability. Our findings reveal that FTO, as an m 6 A demethylase, plays a critical role in promoting PC growth, migration and invasion, suggesting that FTO may be a potential therapeutic target for treating PC.

Pancreatic cancer (PC) is a lethal type of cancer for which effective therapies are limited. Long non‑coding RNAs (lncRNAs) represent a critical type of regulator category, mediating the tumorigenesis and development of various tumor types, including PC. However, the expression patterns and functions of numerous lncRNAs in PC remain poorly understood. In the present study, linc01614 was identified as a PC‑related lncRNA. linc01614 was notably upregulated in PC tissues and cell lines and was associated with the poor disease‑free survival of patients with PC according to the analysis of The Cancer Genome Atlas‑derived datasets. Functionally, linc01614 knockdown suppressed PC cell proliferation, migration and invasion in vitro , and inhibited tumor proliferation in vitro and in vivo . Mechanistically, linc01614 overexpression stabilized the level of β‑catenin protein to hyperactivate the WNT/β‑catenin signaling pathway in PC cells. Further analyses revealed that linc01614 bound to GSK‑3β and perturbed the interaction between GSK‑3β and AXIN1, thereby preventing the formation of the β‑catenin degradation complex and reducing the degradation of β‑catenin. In summary, the present findings reveal that linc01614 may function as an oncogene and promote the progression of PC and may thus be considered as a potential therapeutic target in the future.

Objective: Heat shock protein A2 has been reported to be tightly associated with tumorigenesis and tumor progression. This study aimed to determine the oncogenic and immunological roles of Heat shock protein A2 in pancreatic cancer by bioinformatics., Methods: Expression of Heat shock protein A2 in tumorous and normal specimens of pancreatic cancer was analyzed using the Cancer Genome Atlas and the Cancer Genome Atlas + Genotype-Tissue Expression data sets, respectively. Relationships of Heat shock protein A2 expression with immune infiltrates in pancreatic cancer were assessed. Heat shock protein A2-associated coexpressed genes in pancreatic cancer were obtained, followed by the implementation of enrichment analysis., Results: The data demonstrated that Heat shock protein A2 was significantly overexpressed in tumorous samples compared with normal samples. Heat shock protein A2 expression was remarkably positively interrelated with CD8+ T cell, neutrophil, dendritic cell, and macrophage, but not with CD4+ T and B cells. Heat shock protein A2 expression was markedly positively relevant to both cancer-associated fibroblast and endothelial cell. Enrichment data revealed that Heat shock protein A2 was intimately involved in the tumorigenesis and progression of pancreatic cancer., Conclusion: Heat shock protein A2 is upregulated in pancreatic cancer and is closely associated with tumor immunity and aggressive progression.

Human rabies is a serious public health problem that can't be ignored. Rabies immune globulin (RIG) is an indispensable component of rabies post-exposure prophylaxis (PEP). However, current PEP relies on RIG purified from pooled human or equine plasma, which are either in chronic shortage or associated with safety concerns. Monoclonal antibodies have become widely accepted as safer and more cost-effective alternatives to RIG products in recent years. Here, we assessed the neutralization breadth of human monoclonal antibody ormutivimab and its protective efficacy in PEP models. Ormutivimab was able to neutralize a broad panel of Chinese prevalent street RABVs with neutralizing potency form 198-1487.6 IU/mL. Furthermore, ormutivimab offered comparable protection to that with HRIG both at standard doses (20 IU/kg) and higher doses (100 IU/kg and 200 IU/kg). The interference of ormutivimab on vaccine potency was also analyzed and found slightly reduced neutralizing antibody titers similar to HRIG. The broad-spectrum neutralization activities, highly protective potency, and rapid onset of action make ormutivimab an effective candidate for human rabies PEP., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The clinical values of video head impulse test (vHIT), caloric test (CT) and sensory organization test (SOT) at different stages before and after rehabilitation of 30 patients with vestibular neuritis (VN) in Vertigo Center Ward of Air Force Special Medical Center from January 2019 to January 2020 were analyzed and compared. There were 19 males (63.3%) and 11 females (36.7%), respectively, aged 18-68 (44±14) years. After 1 week and 3 months of rehabilitation in VN patients, the results of the three examinations were detached, and the recovery rates among the three observed indicators of each examination were statistically different ( P <0.001). After 1 week of rehabilitation, the total recovery rate of vHIT was 0, which was lower than that of CT (40.0%) and SOT (43.3%) (both P <0.001). After 3 months of rehabilitation, the total recovery rate of vHIT was 13.3%, which was also lower than CT (86.7%) and SOT (80.0%) (both P <0.001). The current study indicates that the results of observed indicators from vHIT, CT and SOT were detached at different stages of VN rehabilitation. Therefore, the clinical significance of different vestibular function examinations is different but complementary.

Background: Heat shock protein A2 (HSPA2) is known to relate to the pathogenesis and progress of cancer. This study aimed to investigate the connection between HSPA2 and early postsurgical relapse of pancreatic cancer (PC)., Methods: Expression of HSPA2 in 85 pairs of cancerous and matched noncancerous samples was determined by immunostaining method. The relationship between HSPA2 expression and early postsurgical recurrence was assessed using logistic regression. The performance and potential application of HSPA2 expression to predict early postsurgical recurrence was evaluated by receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA)., Results: HSPA2 expression in tumor specimens was markedly elevated compared with non-tumor specimens. Logistic regression analysis indicated that HSPA2 upregulation was an independent risk marker for early postsurgical recurrence of PC. ROC curve analysis and DCA demonstrated that both the area under the curve (AUC) and the net benefit of HSPA2 expression were higher than those of other clinicopathologic features in predicting early postsurgical relapse of PC. The combination of HSPA2 expression with other malignant clinicopathologic characteristics had greater AUC and net benefit relative to them alone in predicting early postsurgical recurrence., Conclusions: Upregulated HSPA2 independently predicts early postsurgical recurrence of PC and has superior predictive performance and potential application value when combined with malignant clinicopathologic features. Our findings reveal that HSPA2 is a promising predictor for early postoperative relapse of PC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-262). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Pancreatic ductal adenocarcinoma (PDAC) is the most common tumor subtype of pancreatic cancer, which exhibits poor patient prognosis due to the lack of effective biomarkers in the diagnosis and treatment. The present study aimed to identify the potential biomarkers of PDAC carcinogenesis and progression using three microarray datasets, GSE15471, GSE16515 and GSE28735, which were downloaded from the Gene Expression Omnibus database. The datasets were analyzed to screen out differentially expressed genes (DEGs) in PDAC tissues and adjacent normal tissues. A total of 143 DEGs were identified, including 132 upregulated genes and 11 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional and signaling pathway enrichment analyses were performed on the DEGs, and the Search Tool for the Retrieval of Interacting Genes/Proteins database was used to construct a protein-protein interaction network. The main functions of DEGs include extracellular matrix degradation, and regulation of matrix metalloproteinase activity and the PI3K-Akt signaling pathway. The five hub genes were subsequently screened using Cytoscape software, and survival analysis demonstrated that abnormal expression levels of the hub genes was associated with poor disease-free survival and overall survival. Biological experiments were performed to confirm whether mesenchymal-to-epithelial transition (MET) factors promote the proliferation, migration and invasion of PDAC cells via the PI3K/AKT signaling pathway. In addition, six MET-targeted microRNAs (miRNAs) were identified, four of which had conserved binding sites with MET. Based on the signaling pathway enrichment analysis of these miRNAs, it is suggested that they can affect the progression of PDAC by targeting MET via the PI3K/AKT signaling pathway. In conclusion, the hub genes and miRNAs that were identified in the present study contribute to the molecular mechanisms of PDAC carcinogenesis and progression. They also provide candidate biomarkers for early diagnosis and treatment of patients with PDAC., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Yao et al.)

Background: Hepatocellular carcinoma (HCC) lacks effective treatments and has a poor prognosis. Therefore it is needed to develop more effective drug targets. Kinesin family member 11 (KIF11) has been reported to affect the progression of several cancers, and its high expression associates with the prognosis of patients. However, the relevant mechanisms of KIF11 in HCC progression have not been studied., Method: Through the cancer genome atlas (TCGA) database and immunohistochemical (IHC) staining of patients' specimens, we determined that KIF11 was highly expressed in HCC tissues and associated with prognosis. We established a KIF11 stably depleted hepatoma cell line, through cell-cloning experiments and cell counting kit-8 (CCK-8) assays to detect the effects on proliferation in vitro . The role of KIF11 in promoting cell proliferation was verified in mice., Result: The expression of KIF11 was negatively correlated with the overall survival (OS) and disease-free survival (DFS) and positively correlated with tumor size of HCC patients. KIF11 depletion inhibits cell proliferation and tumor growth in vitro and in vivo. Conclusion . KIF11 can be used as a positive correlation marker for HCC prognosis and served as a potential therapeutic target., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Zhan-Dong Hu et al.)

Background: Panax notoginseng Saponins (PNS) is used as a traditional Chinese medicine for ischemic stroke and cardiovascular disease; it has been proven to possess anticancer activity recently., Objective: In this study, we aimed to explore the curative anticancer effect and potential mechanisms of PNS in pancreatic cancer cells., Methods: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay, respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting., Results: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem., Conclusion: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This study evaluated whether obese male mice exposed to di-(2-ethylhexyl) phthalate (DEHP) showed synergistic effects on testosterone levels and the potential underlying mechanism., Methods: Forty-eight male mice were assigned to six groups for 12-week treatments as follows: normal, DEHP100, diet-induced obesity (DIO), DIO + DEHP30, DIO + DEHP100, and DIO + DEHP300. Serum hormone levels, including testosterone (T), luteinizing hormone (LH), and leptin, were detected by ELISA. The levels of Ob-R, kisspeptin, and GPR54 protein expression in hypothalamus and testicular tissues were measured by western blot., Results: There were significantly lower levels of serum T and LH, higher levels of serum leptin and Ob-R, and kisspeptin and GPR54 protein expression were reduced in hypothalamus and testicular tissues in the DIO and DEHP groups compared with controls. Moreover, serum T and leptin levels were more severe in the combined DIO and DEHP exposure group than in the single exposure groups. Serum LH levels and GPR54 expression in the testis were significantly decreased in DIO + DEHP300 mice compared with DIO mice (p < 0.05)., Conclusion: Obesity- and DEHP-only exposure had adverse effects on testosterone levels in mice, which may be due to high leptin levels and decreased Ob-R, kisspeptin, and GPR54 expression. Obesity combined with DEHP exposure had an additive adverse effect on testosterone levels in mice. One of the potential mechanisms is higher leptin levels and decreased GPR54 expression in the testes.

MYB transcription factors (TFs) play important roles in the plant's response to abiotic stress. In this study, we cloned a novel MYB TF gene from Vaccinium corymbosum (blueberry) using rapid amplification of cDNA ends (RACE). The cDNA contained a 798-bp open reading frame that encodes a 265-amino acid protein. VcMYB4a possessed a C2/EAR-repressor motif domain and phylogenetic analysis showed that it clustered into a subgroup 4 with six Arabidopsis thaliana MYBs. Quantitative RT-PCR analysis demonstrated that VcMYB4a expression was downregulated by salt, drought, and cold treatment, but was induced by freezing and heat. Overexpression of VcMYB4a in blueberry callus enhanced sensitivity to salt, drought, cold, freezing, and heat stress. These results indicate that VcMYB4a may be an important repressor of abiotic stress in blueberry., 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 © 2020 Elsevier B.V. All rights reserved.)

Background: The Foxo3 gene, belonging to the forkhead family, is one of the classes of transcription factors characterized by a forkhead DNA-binding domain, which usually considered being a cancer suppressor gene. Circ-Foxo3 is a circular structure which connects the 3'end to the 5'end. Scholars detected that circ-Foxo3 could compete with Foxo3 for binding to some miRNAs., Methods: In this study, we will test the expression of Foxo3 and circ-Foxo3 in de novo acute myeloid leukemia (AML) patients to explore the relationship between Foxo3 gene and circ-Foxo3. All the de novo AML samples and normal control samples was measured by real-time quantitative PCR. A receiver operating characteristic curve was conducted to differentiate AML patients from control people. Association of Foxo3 expression and overall survival was conducted by Kaplan-Meier survival analysis., Results: We found that the expression of Foxo3 gene in de novo patients was significantly lower than control samples (P = 0.009). Meanwhile, circ-Foxo3 also expressed lower in de novo AML patients than in control samples (P = 0.040). In different classifications, this trend could be observed more remarkably. In non-M3 patients, the Foxo3 high patients' survival time was longer than Foxo3 low patients (P = 0.002). Besides, in non-favorable risk groups, patients with low expression of Foxo3 had longer survival time than Foxo3 high patients (P = 0.004). Furthermore, in normal Karyotypic patients, the overall survival time of patients with high-expressed Foxo3 was significantly longer than those with low expression (P = 0.034). Besides, Pearson analysis was also conducted between these two genes in AML patients. Results revealed that they were positively correlated (R = 0.63, P < 0.001)., Conclusion: In conclusion, we found that low expression of circ-Foxo3 and Foxo3 were frequent in AML patients, and patients with high expression of Foxo3 often had a trend of better prognosis.

Background: Chronic pruritus is defined as itch lasting for greater than six weeks. Pruritus is a burdensome manifestation of several internal and external disease states with a significant impact on quality of life. Dupilumab has shown promise in treating a number of conditions including atopic dermatitis (AD) and asthma. Its success in reducing pruritus in AD has generated interest regarding its potential application in other pruritic conditions, such as chronic pruritus of unknown origin, uremic pruritus, and pruigo nodularis., Methods: In this retrospective analysis, we present a series of 20 recalcitrant pruritus patients seen at a tertiary center treated with off-label dupilumab at standard AD dosing., Results: Dupilumab was successful at reducing itch in all treated patients, leading to complete resolution in 12/20 patients and an overall mean NRSi reduction of 7.55. Dupilumab was well tolerated with no significant adverse effects., Conclusions: Our case series suggests dupilumab may be a safe and efficacious therapeutic option in several pruritic conditions and demonstrates the need for further studies to better ascertain its place in the pruritus treatment armamentarium., Competing Interests: Lisa L. Zhai, Kevin T. Savage, Connie C. Qiu, Annie Jin and Rodrigo Valdes-Rodriguez have no conflicts. Nicholas K. Mollanazar reports serving as an investigator in trials sponsored by Sanofi and Regeneron Pharmaceuticals. No other disclosures are reported.

FUS1 is a tumor suppressor gene that has been found to be frequently lost in a variety of solid tumors. In this study, we aimed to investigate the expression status of the FUS1 gene in acute myeloid leukemia (AML), as well as its clinical significance. We further explored the correlation between the expression of FUS1 and miR-378 in AML. We detected expression of the FUS1 transcript in bone marrow mononuclear cells from 23 controls and 158 newly diagnosed AML patients by real-time quantitative polymerase chain reaction. Downregulated FUS1 expression was found in 139 out of 158 (87.97%) AML cases; this rate was significantly lower than that in all 23 controls (p = 0.012). Receiver operating characteristic curve analysis revealed that the FUS1 transcript level could discriminate AML patients from controls effectively (area under the ROC curve = 0.663). Kaplan-Meier analysis demonstrated that non-M3-AML patients with a low FUS1 expression had a shorter overall survival (p = 0.049) and leukemia-free survival (p = 0.051) than those with a high FUS1 expression. Furthermore, we studied the correlation between the expression of FUS1 and miR-378 in 53 newly diagnosed AML patients. We found that the correlation coefficient was -0.346, which showed that FUS1 and miR-378 were negatively correlated in AML patients (p = 0.011). These results indicate that the low expression of FUS1 is a common molecular event in AML., (© 2018 S. Karger AG, Basel.)

Chemerin is dysregulation in numerous solid cancers. However, only little is known about the role of chemerin in acute myeloid leukemia (AML). In this study, we aimed to investigate the expression and clinical significance of recently described chemerin in acute myeloid leukemia (AML). The expression of chemerin in 149 patients with de novo AML and 35 normal controls was quantified by Real-time quantitative PCR (RQ-PCR). Chemerin was down-expressed in AML compared with controls (P=0.042). A receiver operating characteristic (ROC) curve revealed that chemerin expression could differentiate patients with AML from control subjects (AUC=0.611, 95% CI: 0.490-0.732; P=0.042) respectively. The cohort of AML patients was divided into two groups according to the cut-off value of 0.0826 (79% sensitivity and 54% specificity, respectively). In addition, the AML patients with low chemerin expression had significantly shorter overall survival (OS) than those with high chemerin expression (P=0.049). Moreover, multivariate survival analysis confirmed that chemerin was an independent prognostic factor for AML patients. In conclusion, downregulation of chemerin might be a useful diagnostic and prognostic factor for AML patients., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Objective: The aim of this study was to describe the distribution of neck-shoulder symptoms among middle school students, and to explore its influence factors. Methods: A cross-sectional survey was conducted on 24 middle schools in Shenyang, Zhengzhou and Shenzhen by purposive sampling method. In each middle school, 3 to 4 classes were selected from each grade all the students in the selected class would be recruited to the survey to investigate the demographic characteristics, neck-shoulder symptoms, physical exercise time, academic stress, screen behavior, sedentary behavior and other information by questionnaire. A total of 10 566 questionnaires were issued and 10 270 valid questionnaires were withdrawn. The prevalence of neck-shoulder symptoms among students were compared by different characteristics. Logistic regression models were applied to examine influencing factors associated with neck-shoulder symptoms. Results: The prevalence of neck-shoulder symptoms among middle school students was 19.2% (1 968/10 270), while it was 22.6% (1 137/5 039) among girls and 15.9% (831/5 231) among boys; the difference showed statistical significance ( P< 0.001). The prevalence of neck-shoulder symptoms was separately 13.3% (253/1 901) in seventh grade, 16.8% (326/1 942) in eighth grade, 18.5% (299/1 617) in ninth grade, 21.8% (417/1 915) in sophomore, 21.4% (345/1 611) in junior, 25.5% (328/1 284) in senior; the difference showed statistical significance ( P< 0.001). The multivariate logistic regression analysis showed that in the last 3 months, students who always playing mobile phone ≥40 min continuously ( OR= 4.66, 95 %CI: 3.95-5.49), watching TV ≥40 min continuously ( OR= 4.01, 95 %CI: 3.39-4.73), using computer ≥40 min continuously ( OR= 3.61, 95 %CI: 3.09-4.23), doing homework ≥60 min continuously ( OR= 3.25, 95 %CI: 2.79-3.79), the average daily sitting time ≥10 h ( OR= 4.95, 95 %CI: 4.25-5.77), and always sitting ≥90 min continuously ( OR= 5.18, 95 %CI: 4.42-6.06) were risk factors of neck-shoulder symptoms. Conclusion: The prevalence of neck-shoulder symptoms was high among middle school students in China, especially girls in senior grades. Long time, high frequency video behaviors and sedentary behaviors were related to the occurrence of neck-shoulder symptoms among middle school students.

Objective: To examine the relationship between the prevalence of self-reported myopia and outdoor activities among middle school students and to explore the influence factors of the self-reported myopia. Methods: A total of 12 979 participants were recruited from junior and senior middle school students in in Shenzhen, Nanchang, Zhengzhou and Shenyang by random cluster sampling method between December 2015 and March 2016. All participants completed an anonymous questionnaire to collect the information of demographic characteristics, self-reported myopia, outdoor activities, etc. 12 603 out of 12 979 copies of questionnaire were valid. The prevalence of self-reported myopia was compared among middle school students with different characteristics. Logistic regression models were used to analyze the relationship between myopia and outdoor activities. Results: The prevalence of self-reported myopia among middle school students was 69.6% (8 766/12 603); which was separately 52.1% (1 216/2 335) in seventh grader, 61.6% (1 459/2 369) in eighth grader, 69.0%(1 470/2 129) in ninth grader, 80.0% (1 812/2 265) in freshmen, 79.4% (1 622/2 042) in sophomore, and 81.1%(1 187/1 463) in junior. The prevalence of self-reported myopia showed an increasing trend with the increase of grade (χ(2)=639.67, P< 0.001). The prevalence of self-reported myopia was separately 63.5%(4 927/7 756) in non-myopic parents group, 78.0%(2 664/3 415)in either myopic parent group, and 82.1%(1 175/1 432) in both myopic parents group(χ(2)=328.28, P< 0.001). Outdoor activities were associated with self-reported myopia. Binary logistic regression analysis showed that the risk of self-reported myopia was significantly increased by always staying at home in extracurricular time among the middle school students ( OR= 1.58, 95 %CI: 1.36-1.82). The risk of self-reported myopia were significantly decreased by always physical exercise and recreational activities after school among middle school students: the ORs were separately 0.67 (95 %CI: 0.57-0.78) for physical exercise and 0.77 (95 %CI: 0.64-0.92) for recreational activities. After stratified analysis by the parents' myopia status, in non-myopic parents group, exercise and recreational activities after school among middle school students decreased the risk of myopia: the ORs were separately 0.68 (95 %CI: 0.55-0.82) for physical exercise and 0.76 (95 %CI: 0.61-0.95) for recreational activities; in either myopic parent group, OR (95 %CI ) were separately 0.65 (0.47-0.90) and 0.68 (0.47-0.98). Conclusion: Outdoor activities was negatively associated with self-reported myopia among middle school students. However, the parents' myopia status may affect the protective effect.

Heat shock-related 70-kDa protein 2 (HSPA2) is known to correlate with tumor development and progression. This work aimed to determine the expression and prognostic roles of HSPA2 in pancreatic carcinoma. Tumor and their corresponding non-tumor tissues were obtained from 80 patients with pancreatic carcinoma. HSPA2 expression in tumor and non-tumor tissues was evaluated by immunohistochemistry. Expression of vascular endothelial growth factor (VEGF) and CD31 in tumor tissues were also evaluated by immunostaining. The relationships of HSPA2 with clinicopathological data, tumor angiogenesis and prognosis were analyzed. The results showed that HSPA2 expression was significantly elevated in tumor tissues compared with adjacent non-tumor tissues (P < 0.05). High HSPA2 expression was significantly associated with aggressive clinicopathological characteristics. HSPA2 staining was positively correlated with VEGF (r = 0.466, P < 0.001) and microvessel density (MVD) (r = 0.366, P = 0.001) in tumor tissues. Patients with high HSPA2 expression showed worse relapse-free survival (RFS) (P < 0.001) and overall survival (OS) (P < 0.001) than those with low HSPA2 expression. Multivariate analysis indicated that high HSPA2 expression was an independent predictor for poor RFS (P < 0.001) and OS (P = 0.001). Taken together, overexpressed HSPA2 is correlated with tumor angiogenesis and poor prognosis in pancreatic carcinoma. HSPA2 may play an important role in tumor progression, and serve as a potential biomarker for the prediction of adverse prognosis in pancreatic carcinoma., (Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: This study was intended to investigate the expression status of Vimentin 2p (VIM 2p), a pseudogene of Vimentin, and further analyze its clinical significance in AML patients., Methods: Real-time quantitative PCR (RQ-PCR) was employed to explore the expression status of VIM 2p in 128 patients with de novo AML and 36 healthy controls., Results: The expression level of VIM 2p was significantly decreased compared with healthy controls (P< 0.001). The patients with low VIM 2p expression were identified in 93 of 128 (73%) of AML patients. No significant differences could be observed in sex, age, blood parameters, FAB/WHO subtypes, karyotype risks and ten gene mutations (FLT3-ITD, NPM1, C-KIT, IDH1/IDH2, DNMT3 A, C/EBPA, N/K-RAS and U2AF1) between VIM 2p low-expressed and high-expressed patients (P> 0.05). Patients with low VIM 2p expression had significantly shorter overall survival (OS) than those with high VIM 2p expression in whole AML cases (median 7 vs. 13 months, respectively, P= 0.032), besides cytogenetically normal AML (CN-AML) and non-M3 AML cohort (P= 0.042 and 0.045, respectively)., Conclusions: These findings indicate that VIM 2p down-regulation is a common event in AML and may be associated with poor clinical outcome.

Myopia has become a major health problem on global scale due to its increasing high prevalence in the past few decades and gradual younger onset age. Accumulated epidemiological surveys have shown that decreased time of exposure to sunlight would be an inducement for the development of myopia. Increasing time spent outdoors and exposure to sunlight might be the most cost-effective and effective measure for children to prevent myopia. This paper summarizes the progress in research of the association between sunlight exposure and myopia in children and its mechanisms to provide new clues for the research on myopia prevention and control.

Objective: Matrix metalloproteinase (MMP)-19 and MMP-20 are important members of the MMP family, and their roles in tumor survivorship and progression are continually reported. This work aimed to determine the expression and prognostic significance of MMP-19 and MMP-20 in pancreatic ductal adenocarcinoma (PDAC)., Methods: Immunohistochemistry was used to investigate the levels of MMP-19 and MMP-20 expression in carcinoma tissues and paracancerous tissues from 102 PDAC patients., Results: The MMP-19 and MMP-20 were, respectively, expressed in 71.6% (73/102) and 70.6% (72/102) of carcinoma tissues, and the expression was positively correlated (r = 0.643, P < 0.001). High-level expression of MMP-19 and MMP-20 was strongly correlated with aggressive clinicopathological characteristics. Kaplan-Meier analysis showed that high-level expression of MMP-19 and MMP-20 was significantly associated with decreased event-free survival (P < 0.001) and overall survival (P < 0.001). Multivariate analysis showed that high-level expression of MMP-19 could act as an independent predictive biomarker for poor event-free survival and overall survival., Conclusions: Levels of MMP-19 and MMP-20 expression are significantly increased in PDAC. High-level expression of MMP-19 and MMP-20 is closely correlated to progression and prognosis of PDAC, and these may be considered as promising markers for unfavorable prognoses.

The BMI1P1 levels of 144 de novo AML patients and 36 healthy donors were detected by real-time quantitative PCR (RQ-PCR). BMI1P1 was significantly down-regulated in AML compared with control (P < 0.001). A receiver operating characteristic (ROC) curve revealed that BMI1P1 expression could differentiate patients with AML from control subjects (AUC = 0.895, 95% CI: 0.835-0.954, P < 0.001). The percentage of blasts in bone marrow (BM) was significantly lower in BMI1P1 high-expressed group versus low-expressed group (P = 0.008). BMI1P1 high-expressed cases had significantly higher complete remission (CR) than BMI1P1 low-expressed cases (P = 0.023). Furthermore, Kaplan-Meier demonstrated that both whole AML cohort and non-M3-AML patients with low BMI1P1 expression showed shorter leukemia free survival (LFS, P = 0.002 and P = 0.01, respectively) and overall survival (OS, P < 0.001 and P = 0.011, respectively) than those with high BMI1P1 expression. Multivariate analysis also showed that BMI1P1 over-expression was an independent favorable prognostic factor for OS in both whole and non-M3 cohort of AML patients (HR = 0.462, 95% CI = 0.243-0.879, P = 0.019 and HR = 0.483, 95% CI = 0.254-0.919, P = 0.027). To further investigate the significance of BMI1P1 expression in the follow-up of AML patients, we monitored the BMI1P1 level in 26 de novo AML patients and found that the BMI1P1 level increased significantly from the initial diagnosis to post-CR (P < 0.001). These results indicated that BMI1P1 might contribute to the diagnosis of AML and the assessment of therapeutic effect., Competing Interests: None.

The purpose of this study was to investigate the expression status of Dual-Specificity Phosphatase 5 Pseudogene 1 (DUSP5P1) and its clinical relevance in patients with acute myeloid leukemia (AML). Real-time quantitative PCR (RQ-PCR) was performed to detect the status of DUSP5P1 expression in 89 patients with de novo AML and 24 normal controls. The level of DUSP5P1 expression was significantly up-regulated in AML compared to controls (P=0.031). The patients with high expression of DUSP5P1 had higher percentage of blasts in bone marrow (BM) than those without high expression (P=0.027). The occurrence rate of DUSP5P1 high expression was significantly higher in M1 (2/8, 25%) and M2 subtypes (9/33, 27%) than in M3 subtype (0/17, 0%) (P=0.034). At the same time, the frequency of DUSP5P1 high expression in patients with intermediate (13/53, 24%) and poor karyotypes (5/11, 45%) was significantly higher than that in patients with favorable karyotype (0/21, 0%) (P=0.003). Meanwhile, DUSP5P1 high-expressed patients had significantly shorter overall survival (OS) than those with low expression (median 4.5 vs. 10.5 months, respectively, P=0.038). Our findings indicated that high expression of DUSP5P1 may identify high-risk AML patients and is associated with poor prognosis in AML.

In recent years, many researches have shown that OCT4 is overexpressed in both germ cell tumors and somatic cancers. Meanwhile, OCT4 has relationship with poor prognosis in a lot of solid tumors, such as hepatocellular carcinoma, gastric cancer, and esophageal cancer. In our study, we investigated the expression status of OCT4 and its clinical significance in patients with acute myeloid leukemia (AML) using real-time quantitative PCR. The receiver operating characteristic (ROC) curve reveals that the level of OCT4 expression could be available for a potential diagnostic biomarker for differentiating AML from controls with an area under the ROC curve (AUC) of 0.915 (95 % confidence interval (CI) 0.837-0.992; P < 0.001). At the cutoff value of 0.56, the sensitivity and the specificity are 75.9 and 81.2 %, respectively. The amount of white blood cell (WBC) of patients with high OCT4 expression is higher than that of patients with low OCT4 expression (18.2 × 10(9) versus 2.7 × 10(9) L(-1), P = 0.001). Among those patients who are less than 70 years old, patients with OCT4 high expression have significantly shorter overall survival (OS) than those without OCT4 high expression (P = 0.048). These findings suggest that OCT4 high expression is a common event and may have an adverse impact on prognosis in AML.

Matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 are known to influence tumor angiogenesis and progression. This work aimed to describe the levels of MMP-2 and TFPI-2 expression associated with tumor angiogenesis and early postoperative recurrence in patients with pancreatic carcinoma. Expression of MMP-2 and TFPI-2 in carcinoma tissues and paracarcinomatous tissues was assayed by immunostaining. Expression of vascular endothelial growth factor (VEGF) and CD34 in tumor tissues was also assayed by immunostaining. The correlations of MMP-2 and TFPI-2 with VEGF, microvessel density (MVD), and early postoperative recurrence were analyzed. The results showed that MMP-2 expression was significantly increased (P < 0.05) and TFPI-2 expression was significantly decreased (P < 0.001) in carcinoma tissues compared with paracarcinomatous tissues. MMP-2 expression was positively correlated with VEGF (r = 0.594, P < 0.001) and MVD (r = 0.432, P < 0.001) in carcinoma tissues. TFPI-2 expression was negatively correlated with VEGF (r = -0.654, P < 0.001) and MVD (r = -0.360, P < 0.001) in carcinoma tissues. Multivariate logistic regression analysis showed that up-regulated MMP-2 and down-regulated TFPI-2 were independent predictors of early postoperative recurrence of pancreatic carcinoma. Receiver operating characteristic curve analysis showed that the combination of MMP-2 and TFPI-2 was a reliable predictive model of early recurrence. We conclude that increased MMP-2 expression and reduced TFPI-2 expression are closely linked to angiogenesis and early postoperative recurrence of pancreatic carcinoma. Immunohistochemical assay of MMP-2 and TFPI-2 may be useful for predicting early relapse of pancreatic carcinoma after surgery.

Background: Dysregulation of miR-675 has been found in a variety of solid tumors. MiR-675 has been suggested as having both oncogenic and tumor suppression properties in cancer. However, there is no evidence whether miR-675 is involved in breast cancer. The objective of this study was to evaluate the expression status of miR-675 and its clinical relevance in breast cancer patients., Methods: The expression level of miR-675 was detected in 100 breast cancer patients and 38 cancer-free controls using real-time quantitative PCR. The clinicopathological characteristics of miR-675 in breast cancer were also investigated. All statistical analyses were performed using SPSS 20.0., Results: The study showed that miR-675 was significantly up-regulated in breast cancer patients compared with controls (P < 0.01). There was no significant difference in age, lymph nodes stage, ER status and PR status between patients with and without miR-675 over-expression (P > 0.05). The frequency of miR-675 over-expression was higher in the patients of histological grade I-II than in others (50% versus 9%, P = 0.011). The expression level of miR-675 had a high correlation with miR-24/93/98/378 in breast cancer patients., Conclusions: Taken together, our study demonstrated that miR-675 in formalin-fixed paraffin-embedded (FFPE) tissues might serve as a good source for biomarker discovery and breast cancer validation.

To investigate the expression of homeobox B (Hoxb)-13 and analyze its relationship with tumor angiogenesis, epithelial-mesenchymal transition (EMT)-associated markers (E-cadherin and vimentin), clinicopathologic data and prognosis in pancreatic carcinoma. Immunohistochemistry was applied to determine the level of Hoxb-13 expression in tumor tissues and surrounding non-tumor tissues from 85 subjects with pancreatic carcinoma. Besides, vascular endothelial growth factor (VEGF), CD31, E-cadherin and vimentin were also detected in tumor tissues by immunostaining. We found that the level of Hoxb-13 expression was significantly higher in pancreatic carcinoma tissues than in paracarcinomatous tissues (P < 0.05). Hoxb-13 staining was positively correlated with VEGF (r = 0.429, P < 0.001) and microvessel density (MVD) (r = 0.454, P < 0.001). Likewise, Hoxb-13 staining was positively correlated with vimentin (r = 0.448, P < 0.001); while it was negatively correlated with E-cadherin (r = -0.405, P < 0.001). High Hoxb-13 expression was associated with aggressive clinicopathological characteristics, worse disease-free survival (DFS) (P < 0.001) and worse overall survival (OS) (P < 0.001). Multivariate analysis showed that Hoxb-13 was an independent predictor for poor DFS (P < 0.001) and OS (P = 0.002). In conclusion, our data show that overexpressed Hoxb-13 is correlated with tumor angiogenesis, aberrant expression of EMT-associated markers and aggressive clinicopathological characteristics, and serves as a promising marker for unfavourable prognosis in pancreatic carcinoma.