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Background: The comprehensive expression level and potential molecular role of Cyclin A2 (CCNA2) in uterine corpus endometrial carcinoma (UCEC) remains undiscovered., Methods: UCEC and normal endometrium tissues from in-house and public databases were collected for investigating protein and messenger RNA expression of CCNA2. The transcription factors of CCNA2 were identified by the Cistrome database. The prognostic significance of CCNA2 in UCEC was evaluated through univariate and multivariate Cox regression as well as Kaplan-Meier curve analysis. Single-cell RNA-sequencing (scRNA-seq) analysis was performed to explore cell types in UCEC, and the AUCell algorithm was used to investigate the activity of CCNA2 in different cell types., Results: A total of 32 in-house UCEC and 30 normal endometrial tissues as well as 720 UCEC and 165 control samples from public databases were eligible and collected. Integrated calculation showed that the CCNA2 expression was up-regulated in the UCEC tissues (SMD = 2.43, 95% confidence interval 2.23∼2.64). E2F1 and FOXM1 were identified as transcription factors due to the presence of binding peaks on transcription site of CCNA2. CCNA2 predicted worse prognosis in UCEC. However, CCNA2 was not an independent prognostic factor in UCEC. The scRNA-seq analysis disclosed five cell types: B cells, T cells, monocytes, natural killer cells, and epithelial cells in UCEC. The expression of CCNA2 was mainly located in B cells and T cells. Moreover, CCNA2 was active in T cells and B cells using the AUCell algorithm., Conclusion: CCNA2 was up-regulated and mainly located in T cells and B cells in UCEC. Overexpression of CCNA2 predicted unfavorable prognosis of UCEC., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Previous studies show that notoginsenoside R1 (NG-R1), a novel saponin isolated from Panax notoginseng, protects kidney, intestine, lung, brain and heart from ischemia-reperfusion injury. In this study we investigated the cardioprotective mechanisms of NG-R1 in myocardial ischemia/reperfusion (MI/R) injury in vivo and in vitro. MI/R injury was induced in mice by occluding the left anterior descending coronary artery for 30 min followed by 4 h reperfusion. The mice were treated with NG-R1 (25 mg/kg, i.p.) every 2 h for 3 times starting 30 min prior to ischemic surgery. We showed that NG-R1 administration significantly decreased the myocardial infarction area, alleviated myocardial cell damage and improved cardiac function in MI/R mice. In murine neonatal cardiomyocytes (CMs) subjected to hypoxia/reoxygenation (H/R) in vitro, pretreatment with NG-R1 (25 μM) significantly inhibited apoptosis. We revealed that NG-R1 suppressed the phosphorylation of transforming growth factor β-activated protein kinase 1 (TAK1), JNK and p38 in vivo and in vitro. Pretreatment with JNK agonist anisomycin or p38 agonist P79350 partially abolished the protective effects of NG-R1 in vivo and in vitro. Knockdown of TAK1 greatly ameliorated H/R-induced apoptosis of CMs, and NG-R1 pretreatment did not provide further protection in TAK1-silenced CMs under H/R injury. Overexpression of TAK1 abolished the anti-apoptotic effect of NG-R1 and diminished the inhibition of NG-R1 on JNK/p38 signaling in MI/R mice as well as in H/R-treated CMs. Collectively, NG-R1 alleviates MI/R injury by suppressing the activity of TAK1, subsequently inhibiting JNK/p38 signaling and attenuating cardiomyocyte apoptosis., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: Pancreatic adenocarcinoma (PAAD) is a malignant tumor responsible for a heavy disease burden. Previously, only one pan-cancer study of Transmembrane channel-like protein 5 (TMC5) showed that TMC5 was highly expressed in PAAD, but the results lacked comprehensive verification, and the mechanism of TMC5 in PAAD was still unclear., Methods: For exploring the expression and clinical value of TMC5 in PAAD better, we adopted a comprehensive evaluation method, using internal immunohistochemistry (IHC) data combined with microarray and RNA-sequencing data collected from public databases. The single cell RNA-sequencing (scRNA-seq) data were exploited to explore the TMC5 expression in cell populations and intercellular communication. The potential mechanism of TMC5 in PAAD was analyzed from the aspects of immune infiltration, transcriptional regulation, function and pathway enrichment., Results: Our IHC data includes 148 PAAD samples and 19 non-PAAD samples, along with the available microarray and RNA-sequencing data (1166 PAAD samples, 704 non-PAAD samples). The comprehensive evaluation results showed that TMC5 was evidently up-regulated in PAAD (SMD = 1.17). Further analysis showed that TMC5 was over-expressed in cancerous epithelial cells. Furthermore, TMC5 was up-regulated in more advanced tumor T and N stages. Interestingly, we found that STAT3 as an immune marker of Th17 cells was not only positively correlated with TMC5 and up-regulated in PAAD tissues, but also the major predicted TMC5 transcription regulator. Moreover, STAT3 was involved in cancer pathway of PAAD., Conclusion: Up-regulated TMC5 indicates advanced tumor stage in PAAD patients, and its role in promoting PAAD development may be regulated by STAT3., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Little is known about the relationship between integrin subunit alpha V (ITGAV) and cancers, including small cell lung cancer (SCLC)., Methods: Using large sample size from multiple sources, the clinical roles of ITGAV expression in SCLC were explored using differential expression analysis, receiver operating characteristic curves, Kaplan-Meier curves, etc. RESULTS: Decreased mRNA (SMD = - 1.05) and increased protein levels of ITGAV were detected in SCLC (n = 865). Transcription factors-ZEB2, IK2F1, and EGR2-may regulate ITGAV expression in SCLC, as they had ChIP-Seq (chromatin immunoprecipitation followed by sequencing) peaks upstream of the transcription start site of ITGAV. ITGAV expression made it feasible to distinguish SCLC from non-SCLC (AUC = 0.88, sensitivity = 0.78, specificity = 0.84), and represented a risk role in the prognosis of SCLC (p < 0.05). ITGAV may play a role in cancers by influencing several immunity-related signaling pathways and immune cells. Further, the extensive pan-cancer analysis verified the differential expression of ITGAV and its clinical significance in multiple cancers., Conclusion: ITGAV served as a potential marker for prognosis and identification of cancers including SCLC., (© 2022. The Author(s).)

Introduction: We aimed to explore the abnormal expression of dual-specificity protein phosphatase 1 (DUSP1) and its latent molecular mechanisms in ovarian carcinoma (OVCA). Materials and Methods: Two clinical cohorts collected from two different hospitals were used to evaluate the expression of DUSP1 protein in OVCA tissues. RNA-sequencing and microarray datasets were utilised to verify DUSP1 expression at mRNA levels in both OVCA tissues and in the peripheral blood of OVCA patients. Furthermore, an integrated calculation was performed to pool the standard mean difference (SMD) from each cohort in order to comprehensively assess the expression of DUSP1 in OVCA. Furthermore, we examined the relationship among DUSP1, tumour microenvironment (TME), and chemotherapy resistance in OVCA. Moreover, we used pathway enrichment analysis to explore the underlying mechanisms of DUSP1 in OVCA. Results: A pooled SMD of -1.19 (95% CI [-2.00, -0.38], p = 0.004) with 1,240 samples revealed that DUSP1 was downregulated in OVCA at both mRNA and protein levels. The area under the receiver operating characteristic curve of 0.9235 indicated the downregulated DUSP1 in peripheral blood may have a non-invasive diagnostic value in OVCA. Through six algorithms, we identified that DUSP1 may related to tumour-infiltrating T cells and cancer associated fibroblasts (CAFs) in OVCA. Pathway enrichment demonstrated that DUSP1 might participate in the mitogen-activated protein kinase (MAPK) signalling pathway. Furthermore, DUSP1 may have relations with chemotherapy resistance, and a favourable combining affinity was observed in the paclitaxel-DUSP1 docking model. Conclusion: DUSP1 was downregulated in OVCA, and this decreasing trend may affect the infiltration of CAFs. Finally, DUSP1 may have a targeting relation with paclitaxel and participate in MAPK signaling pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liang, He, Luo, Huang, Li, Zhong, Chen, Huang, Shi, Wei, Zeng, Zeng and Chen.)

Background: Primary ovarian lymphoma has been difficult to diagnose clinically and pathologically due to its rare incidence and non-specific clinical symptoms., Case Presentation: A 75-year-old female patient was reported in this study. The patient had a six-month history of changes in bowel habits, with occasional black feces and paroxysmal pain in the abdomen. The computed tomography scan of the pelvic cavity illustrated that rectal cancer and sigmoid colon adenocarcinoma invaded the lower part of the right-side ureter. The patient was once treated with excision of part of small intestine, fallopian tube and ovary, and uterus. The pathological examination of these excised tissues, combined with the immunohistochemistry, confirmed that the female patient suffered from primary ovarian diffuse large B-cell lymphoma (DLBCL), and the lymphoma had invaded the entire right-side ovary tissues, serous membranes on the posterior surface of the uterus, and the wall of small intestine., Conclusion: Few reports were available regarding the primary ovarian DLBCL. The initial symptom of the patient was the changes in bowel habits, which had not been reported beforehand. Hopefully, this case could helpfully render the early diagnosis possible, and increase clinical understanding of primary ovarian DLBCL, which would thereby reduce the chance of misdiagnosis., (© 2022. The Author(s).)

In this study, we aim to identify the clinical significance of basonuclin 1 ( BNC1 ) expression in ovarian carcinoma (OV) and to explore its latent mechanisms. Via integrating in-house tissue microarrays, gene chips, and RNA-sequencing data, we explored the expression and clinical value of BNC1 in OV. Immunohistochemical staining was utilized to confirm the protein expression status of BNC1. A combined SMD of -2.339 (95% CI : -3.649 to -1.028, P  <   0.001) identified that BNC1 was downregulated based on 1346 samples, and the sROC (AUC = 0.93) showed a favorable discriminatory ability of BNC1 in OV patients. We used univariate and multivariate Cox regulation to evaluate the prognostic role of BNC1 for OV patients, and a combined hazard ratio of 0.717 (95% CI : 0.445-0.989, P  <   0.001) revealed that BNC1 was a protective factor for OV. Furthermore, the fraction of infiltrating naive B cells, memory B cells, and other immune cells showed statistical differences between the high- and low- BNC1 expression groups through cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Enrichment analysis showed that BNC1 may have a relationship with immune-related items in OV. By predicting the potential regulatory transcription factors (TFs) of BNC1 , friend leukemia virus integration 1 ( FLI1 ) may be a potential upstream TF of BNC1 . Corporately, a decreasing trend of BNC1 may serve as a tumor suppressor and prognostic biomarker in OV patients. Moreover, BNC1 may take part in immune-related pathways and influence the fraction of tumor-infiltrating immune cells.

The clinicopathological value of microRNA-141-3p (miR-141-3p) and its prospective target genes in endometrial carcinoma (EC) remains unclear. The present study determined the expression level of miR-141-3p in EC via quantitative real-time PCR (RT-qPCR). RT-qPCR showed a markedly higher expression level of miR-141-3p in EC tissues than in non-EC endometrium tissues ( P < 0.0001). The microarray and miRNA-seq data revealed upregulation of miR-141-3p. Integrated analysis based on 675 cases of EC and 63 controls gave a standardized mean difference of 1.737, confirmed the upregulation of miR-141-3p. The Kaplan-Meier survival curve showed that a higher expression of miR-141-3p positively corelated with a poorer prognosis. Combining the predicted targets and downregulated genes in EC, we obtained 271 target genes for miR-141-3p in EC. Two potential targets, PPP1R12A and PPP1R12B, were downregulated at both the mRNA and protein levels. This study indicates that the overexpression of miR-141-3p may play an important part in the carcinogenesis of EC. The overexpression of miR-141-3p may be a risk factor for the prognosis of patients with EC.

This study is aimed at thoroughly exploring the expression status, clinical significance, and underlying molecular mechanism of miRNA-33a-5p in lung squamous cell carcinoma (LUSC). Here, we detected miRNA-33a-5p in 20 samples from patients with LUSCs and 20 matching non-LUSC specimens by in-house quantitative real-time PCR (RT-qPCR). Relationship between miRNA-33a-5p expression and clinicopathological traits was investigated from materials derived from miRNA sequencing and miRNA microarrays. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to evaluate the integrated expression value of miRNA-33a-5p in LUSC. Twelve online platforms were applied to select potential target genes of miRNA-33a-5p. The differentially expressed genes (DEGs) of LUSC and the candidate target genes of miRNA-33a-5p were overlapped to acquire a set of specific genes for further analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interaction (PPI) network. miRNA-33a-5p overexpressed in LUSC was supported by 706 LUSC and 261 non-LUSC samples gathering from RT-qPCR, miRNA-seq, and public miRNA microarrays. The pooled SMD was 0.56 (95% CI: -0.01-1.05), and the area under the curve (AUC) of the SROC was 0.78 (95% CI: 0.74-0.82). A total of 240 genes were identified as potential target genes of miRNA-33a-5p for functional enrichment analyses; the results suggested that these target genes may participate in several vital biological processes that promote the proliferation and progression of LUSC. miRNA-33a-5p may play an essential role in the occurrence and development of LUSC by targeting hub genes (ETS1, EDNRB, CYR61, and LRRK2) derived from the PPI network. In summary, our results indicated that miRNA-33a-5p may contribute as a prospective therapeutic target in LUSC., Competing Interests: The authors declare there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Xiang-Ming Wang et al.)

Background: Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer., Methods: A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Immunohistochemistry was performed for evaluating PLK1 expression between cervical cancer (including cervical squamous cell carcinoma (CESC) and cervical adenocarcinoma) and non-cancer samples. The Expression Atlas database was searched for querying PLK1 expression in different cervical cancer cell lines and different tissues in the context of pan-cancer. Standard mean difference (SMD) was calculated and the summarized receiver's operating characteristics (SROC) curves were plotted for integrated tissue microarrays, exterior high-throughput microarrays and RNA sequencing data as further verification. The effect of PLK1 expression on the overall survival, disease-free survival and event-free survival of cervical cancer patients was analyzed through Kaplan Meier survival curves for cervical cancer patients from RNA-seq and GSE44001 datasets. The gene mutation and alteration status of PLK1 in cervical cancer was inspected in COSMIC and cBioPortal databases. Functional enrichment analysis was performed for genes correlated with PLK1 from aggregated RNA-seq and microarrays., Results: A total of 963 cervical cancer samples and 178 non-cancer samples were collected from in-house tissue microarrays and exterior microarrays and RNA-seq datasets. The combined expression analysis supported overexpression of PLK1 in CESC, cervical adenocarcinoma and all types of cervical cancer (SMD = 1.59, 95%CI [0.56-2.63]; SMD = 2.99, 95%CI [0.75-5.24]; SMD = 1.57, 95% CI [0.85-2.29]) and the significant power of PLK1 expression in distinguishing CESC or all types of cervical cancer samples from non-cancer samples (AUC = 0.94, AUC = 0.92). Kaplan-Meier survival curves showed that the event-free survival rate of cervical cancer patients with higher expression of PLK1 was shorter than that of patients with lower PLK1 (HR = 2.020, P  = 0.0197). Genetic alteration of PLK1 including missense mutation and mRNA low occurred in 6% of cervical cancer samples profiled in mRNA expression. Genes positively or negatively correlated with PLK1 were mainly assembled in pathways such as DNA replication, cell cycle, mismatch repair, Ras signaling pathway, melanoma, EGFR tyrosine kinase inhibitor resistance and homologous recombination ( P  < 0.05)., Conclusions: Here, we provided sufficient evidence of PLK1 overexpression in cervical cancer. The overexpression of PLK1 in cervical cancer and the contributory effect of it on clinical progression indicated the hopeful prospect of PLK1 as a biomarker for cervical cancer., Competing Interests: The authors declare there are no competing interests., (©2020 Gao et al.)

Background: The situation faced by breast cancer patients, especially those with triple-negative breast cancer, is still grave. More effective therapeutic targets are needed to optimize the clinical management of breast cancer. Although collagen type VIII alpha 1 chain (COL8A1) has been shown to be downregulated in BRIP1-knockdown breast cancer cells, its clinical role in breast cancer remains unknown., Methods: Gene microarrays and mRNA sequencing data were downloaded and integrated into larger matrices based on various platforms. Therefore, this is a multi-centered study, which contains 5048 breast cancer patients and 1161 controls. COL8A1 mRNA expression in breast cancer was compared between molecular subtypes. In-house immunohistochemistry staining was used to evaluate the protein expression of COL8A1 in breast cancer. A diagnostic test was performed to assess its clinical value. Furthermore, based on differentially expressed genes (DEGs) and co-expressed genes (CEGs) positively related to COL8A1, functional enrichment analyses were performed to explore the biological function and potential molecular mechanisms of COL8A1 underlying breast cancer., Results: COL8A1 expression was higher in breast cancer patients than in control samples (standardized mean difference = 0.79; 95% confidence interval [CI] 0.55-1.03). Elevated expression was detected in various molecular subtypes of breast cancer. An area under a summary receiver operating characteristic curve of 0.80 (95% CI 0.76-0.83) with sensitivity of 0.77 (95% CI 0.69-0.83) and specificity of 0.70 (95% CI 0.61-0.78) showed moderate capacity of COL8A1 in distinguishing breast cancer patients from control samples. Worse overall survival was found in the higher than in the lower COL8A1 expression groups. Intersected DEGs and CEGs positively related to COL8A1 were significantly clustered in the proteoglycans in cancer and ECM-receptor interaction pathways., Conclusions: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes. Several genes clustered in the proteoglycans in cancer pathway are potential targets for developing effective agents for triple-negative breast cancer., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2020.)

RNA molecules and targeting microRNA (miRNA) have been reported as novel focuses in recent research on breast cancer. This study aimed to probe the expression of FOXO1 in the MDA-MB-231 cell line and to explore the target effects of FOXO1 with hsa-microRNA-204-5p (miR-204) on the biologic behavior of MDA-MB-231 cells. The expression of FOXO1 mRNA and protein in MDA-MB-231 cells were derived and verified from the public databases, literature, and experimental assays, then the downregulation of FOXO1 was confirmed in the MDA-MB-231 cell line. The target binding of FOXO1 and miR-204 was predicted by miRWalk and confirmed by luciferase reporter assays. MiR-204 targeted the 3' untranslated region of FOXO1 and reduced FOXO1 expression in miR-204-transfected cells, resulting in cell growth amplification but inhibition of cell migration and apoptosis, which were assessed using the MTT method, wound healing assays, and flow cytometry, respectively. The protein levels of serine-threonine kinase (AKT), c-jun N-terminal kinase (JNK), extracellular regulatory protein kinase (ERK), and the phosphorylated protein kinases (P-AKT, P-JNK, and P-ERK) were measured by western blot. It was found that AKT, JNK, and ERK remained constant, but P-AKT, P-JNK, and P-ERK were upregulated after miR-204 transfection. In summary, the expression of FOXO1 was downregulated in MDA-MB-231 cells; and the target binding of miR-204 and FOXO1 affected phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signal pathways, leading to different alterations of cellular activity in MDA-MB-231 cells., Competing Interests: None., (IJCEP Copyright © 2020.)

Breast cancer (BC) is the most common cancer worldwide. However, the expression and potential mechanism of miR-375 in BC are still controversial. We first collected microRNA chips and microRNA sequencing data from multiple databases for analyzing the expression level of miR-375, and further exploring the target genes and underlying molecular mechanism in BC. miR-375 in BC was predominantly overexpressed compared with that in normal breast tissues (pooled standard mean difference [SMD] = 0.49; 95 % confidence interval [CI]: 0.24-0.73, p < 0.0001). Meanwhile, the overall pooled area under the curve (AUC) in the summary receiver operating characteristic (SROC) of miR-375 was 0.83 (95 % CI = 0.79-0.86) based on 2928 cases of BC patients and 816 cases of controls, while the diagnostic positive likelihood ratio (DLR) positive and the DLR negative value were 3.90 (95 % CI = 2.46-6.19) and 0.39 (95 % CI = 0.28-0.54), respectively. The hazard ratios (HRs) were 1.29 (95 % CI = 1.04-1.6, P = 0.02) and 1.23 (95 % CI = 0.89-1.7, P = 0.22) for the cohorts of METABRIC and The Cancer Genome Atlas (TCGA). In vitro study demonstrated that miR-375 inhibitor could suppress the cell growth and induce apoptosis of BC cells. A total of 107 overlapping genes from microarrays after miR-375 transfection, the TCGA RNA sequencing, the microarrays of Affymetrix platform, and online predicting software were selected as the prospective targets of miR-375 in BC. Based on Gene Ontology (GO) enrichment analysis, the potential targets of miR-375 were notable for their somatic stem cell division, plasma membrane, and proline-rich region binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway examination demonstrated that the targets were associated with the pathways of prion diseases, proteoglycans in cancer, and focal adhesion. Then, 107 targets of miR-375 in BC were used to construct a protein-protein interaction (PPI) network. Finally, EGFR, PRKCA, PPARA, ADIPOQ, and ITSN1 were found to be the hub genes of miR-375. These targets showed negative correlations with miR-375 level. The upregulated miR-375 might play an essential part in the tumorigenesis and progression of BC., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

The severe damage to health and social burden caused by head and neck squamous cell carcinoma (HNSCC) generated an urgent need to develop novel anti-cancer therapy. Currently, drug repositioning has risen in responses to the proper time as an efficient approach to invention of new anti-cancer therapies. In the present study, we aimed to screen candidate drugs for HNSCC by integrating HNSCC-related pathways from differentially expressed genes (DEGs) and drug-affected pathways from connectivity map (CMAP). We also endeavored to unveil the molecular mechanism of HNSCC through creating drug-target network and protein-to-protein (PPI) network of component DEGs in key overlapping pathways. As a result, a total of 401 DEGs were obtained from TCGA and GTEx mRNA-seq data. Taking the intersection part of 27 HNSCC-related Kyoto Encyclopedia of Genes and Genomes pathways and 33 drug-affected pathways, we retained 22 candidate drugs corresponding to two key pathways (cell cycle and p53 signaling pathways) of the five overlapping pathways. Two of the hub genes (PCNA and CCND1) identified from the PPI network of component DEGs in cell cycle and p53 signaling pathways were defined as the critical targets of candidate drugs with increased protein expression in HNSCC tissues, which was reported by the human protein atlas (HPA) database and cBioPortal. Finally, we validated via molecular docking analysis that two drugs with unknown effects in HNSCC: MG-262 and bepridil might perturb the development of HNSCC through targeting PCNA. These candidate drugs possessed broad application prospect as medication for HNSCC., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Malignant tumors of the digestive tract include esophageal, gastric, and colorectal carcinomas, which all have high global mortality rates. A clinical role for small nuclear RNA (snRNA), a type of small non-coding RNA, has not yet been documented for digestive tract pan-adenocarcinomas. Therefore, the aim of the study was to identify differentially expressed snRNAs and to explore their prognostic implications in pan-adenocarcinomas from the esophagus, stomach, colon, and rectum. The pan-carcinoma RNA-sequencing data of four types of digestive tract cancers with 1, 102 cases obtained from The Cancer Genome Atlas (TCGA) project were analyzed and the differentially expressed snRNAs were evaluated using the edgeR package. The prognostic value of each of the selected snRNAs was determined by univariate and multivariate Cox regression analyses. All the digestive tract pan-adenocarcinomas showed differential expression of three snRNAs: the up-regulated RNU1-106 P and RNU6-850 P and the down-regulated RNU6-529 P. Interestingly, RNU6-101 P appeared to be a risk factor for esophageal adenocarcinoma (ESAD) and RNVU1-4 was potentially a protective factor for stomach adenocarcinoma (STAD) survival. This consistent finding of differential expression of all three snRNAs in all four types of digestive system cancers suggests potential roles for these snRNAs in the tumorigenesis of digestive system cancers. RNU6-101 P could play a pivotal role in the progression of ESAD and RNVU1-4 could perform a protective role in STAD. However, since the current findings were based on RNA-sequencing data mining, more studies are needed for verification., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Breast cancer (BC) is the most common cancer among women worldwide. However, there is insufficient research that focuses on the expression and molecular mechanisms of microRNA (miR)‑204‑5p in BC. In the current study, data were downloaded from the Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena databases. They were then used to undertake a meta‑analysis that leveraged the standard mean difference (SMD) and summarized receiver operating characteristic (sROC) to evaluate the expression of the precursor miR‑204 and mature miR‑204‑5p in BC. Additionally, an intersection of predicted genes, differentially expressed genes (DEGs) from the TCGA database and the GEO database were plotted to acquire desirable putative genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein‑protein interaction (PPI) network analyses were performed to assess the potential pathways and hub genes of miR‑204‑5p in BC. A decreased trend in precursor miR‑204 expression was detected in 1,077 BC tissue samples in comparison to 104 para‑carcinoma tissue samples in the TCGA database. Further, the expression of mature miR‑204‑5p was markedly downregulated in 756 BC tissue samples in comparison to 76 para‑carcinoma tissue samples in the UCSC Xena database. The outcome of the SMD from meta‑analysis also indicated that the expression of miR‑204‑5p was markedly reduced in 2,306 BC tissue samples in comparison to 367 para‑carcinoma tissue samples. Additionally, the ROC and sROC values indicated that miR‑204‑5p had a great discriminatory capacity for BC. In GO analysis, 'cell development', 'cell surface activity', and 'receptor agonist activity' were the most enriched terms; in KEGG analysis, 'endocytosis' was significantly enriched. Rac GTPase activating protein 1 (RACGAP1) was considered the hub gene in the PPI network. In conclusion, miR‑204‑5p may serve a suppressor role in the oncogenesis and advancement of BC, and miR‑204‑5p may have crucial functions in BC by targeting RACGAP1.

Breast cancer (BC) is a kind of malignant cancer that seriously threatens women's health. Research scientists have found that BC occurs as the result of multiple effects of the external environment and internal genetic changes. Cell cycle checkpoint kinase 1 (CHEK1) is a crucial speed limit point in the cell cycle. Alterations of CHEK1 have been found in various tumors but are rarely reported or verified in BC. By mining database information, a large amount of mRNA and protein data was collected and meta-analyzed. Also, in-house immunohistochemistry was carried out to validate the results of the CHEK1 expression levels. Relative clinical features of BC patients were calculated with the CHEK1 expression levels to determine their diagnostic value. The mRNA levels of CHEK1 were higher in 1,089 cases of BC tissues than in 291 cases of non-BC tissues. We observed that the mRNA levels of CHEK1 are related to the clinical stages of BC patients (P = 0.008) and are also significant for overall survival (HR = 1.6, P = 0.0081). Using the immunohistochemistry method, we calculated and confirmed, using Fisher's exact test (P < 0.001), that a high-level CHEK1 protein is exhibited in BC tissues. Overexpressed CHEK1 mRNA promotes the occurrence of BC. Also, up-regulated CHEK1 could serve as an independent risk biomarker in BC patients' prognoses., Competing Interests: None., (IJCEP Copyright © 2019.)

Background and Objectives: Pharmacological control against ovarian serous cystadenocarcinoma has received increasing attention. The purpose of this study was to investigate multi-drug treatments as synergetic therapy for ovarian serous cystadenocarcinoma and to explore their mechanisms of action by the network pharmacology method., Methods: Genes acting on ovarian serous cystadenocarcinoma were first collected from GEPIA and DisGeNET. Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway, Reactome pathway, and Disease Ontology analyses were then conducted. A connectivity map analysis was employed to identify compounds as treatment options for ovarian serous cystadenocarcinoma. Targets of these compounds were obtained from the Search Tool for Interacting Chemicals (STITCH). The intersections between the ovarian serous cystadenocarcinoma-related genes and the compound targets were identified. Finally, the Kyoto Encyclopedia of Genes and Genomes and Reactome pathways in which the overlapped genes participated were selected, and a correspondence compound-target pathway network was constructed., Results: A total of 541 ovarian serous cystadenocarcinoma-related genes were identified. The functional enrichment and pathway analyses indicated that these genes were associated with critical tumor-related pathways. Based on the connectivity map analysis, five compounds (resveratrol, MG-132, puromycin, 15-delta prostaglandin J2, and valproic acid) were determined as treatment agents for ovarian serous cystadenocarcinoma. Next, 48 targets of the five compounds were collected. Following mapping of the 48 targets to the 541 ovarian serous cystadenocarcinoma-related genes, we identified six targets (PTGS1, FOS, HMOX1, CASP9, PPARG, and ABCB1) as therapeutic targets for ovarian serous cystadenocarcinoma by the five compounds. By analysis of the compound-target pathway network, we found the synergistic anti-ovarian serous cystadenocarcinoma potential and the underlying mechanisms of action of the five compounds., Conclusion: In summary, latent drugs against ovarian serous cystadenocarcinoma were acquired and their target actions and pathways were determined by the network pharmacology strategy, which provides a new prospect for medicamentous therapy for ovarian serous cystadenocarcinoma. However, further in-depth studies are indispensable to increase the validity of this study.

Thyroid cancer (TC) is the most common endocrine malignancy, accounting for approximately 90% of all malignancies of the endocrine system. Despite the fact that patients with TC tend to have good prognoses, the high incidence rate and lymph node metastases remain unresolved issues. Autophagy is an indispensable process that maintains intracellular homeostasis; however, the role of autophagy in several steps of the initiation and progression of TC has not yet been elucidated. In this study, we first identified several autophagy-related genes (ARGs) that were provoked in the onset of TC. Subsequently, a bioinformatics analysis hinted that these genes were markedly disturbed in several proliferative signaling pathways. Moreover, we demonstrated that the differentially expressed ARGs were closely related to several aggressive clinical manifestations, including an advanced tumor stage and lymph node metastasis. Our study further selected prognostic ARGs and developed a prognostic signature based on three key genes (ATG9B, BID and B1DNAJB1), which displayed a moderate ability to predict the prognosis of TC. On the whole, the findings of this study demonstrate that ARGs disrupt proliferation-related pathways and consequently lead to aggressive clinical manifestations. These findings provide insight into the potential molecular mechanisms of action of ARGs and their clinical significance, and also provide classification information of potential therapeutic significance.

BACKGROUND miR-490-3p could play vital roles in multiple cancers. However, the role of miR-490-3p in hepatocellular carcinoma (HCC) remains uncertain. In this study, we sought to explore the underlying role of miR-490-3p in HCC. MATERIAL AND METHODS In this study, we explored the clinical role of miR-490-3p in HCC via quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and The Cancer Genome Atlas (TCGA) database. Then, a meta-analysis was performed to evaluate the expression trend and diagnostic value of miR-490-3p in HCC. Furthermore, 12 miRNA prediction algorithms were applied to predict the potential target genes of miR-490-3p. The differentially expressed genes in HCC in the Gene Expression Profiling Interactive Analysis (GEPIA) database were also selected. Additionally, bioinformatics analyses were utilized to investigate the possible functions and pathways of the target genes. RESULTS miR-490-3p was clearly down-regulated in HCC based on RT-qPCR (P=0.002). Consistent with the results of RT-qPCR, miR-490 was more highly expressed in normal liver tissue than in HCC (P<0.001). Additionally, the meta-analysis confirmed the results from RT-qPCR and TCGA. Furthermore, based on the prediction algorithms and GEPIA, a total of 113 genes were selected. According to the bioinformatics analyses, we found that the most remarkably enriched functional terms included protein transport, poly(A) RNA binding, and intracellular organelle part. Additionally, the miR-490-3p target genes were significantly related to the pathways in cancer. CONCLUSIONS We found that miR-490-3p is down-regulated in HCC and is related to genes that have potential tumoral functions. However, the exact mechanism should be confirmed by functional experiments.

Since urothelial cancer associated 1 (UCA1) was discovered in human bladder cancer, it has been reported to be dysregulated expressed in various kinds of solid tumors. But the clinical role and the function of UCA1 in non-small cell lung cancer (NSCLC) remains incompletely understood. In this study, we mined the data of UCA1 expression in NSCLC from Oncomine, Gene expression profiling interactive analysis (GEPIA) and cBioPortal to analyze the contribution of UCA1 in the cancer initiation and progression of NSCLC. We also performed a series of in vitro experiments by using NSCLC cells to confirm the biological function of UCA1 in NSCLC, especially its effect on caspase-3/7 activity and apoptosis through RNA interference experiment. From Oncomine, the UCA1 levels were both up-regulated in lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC), as compared to non-cancerous controls. Higher levels of UCA1 pointed to a poorer overall survival in NSCLC, with the HR being 1.3. Only two genetic alterations, including amplification and deep deletion, were observed for UCA1 as provided by cBioPortal. Both MTS and Cell Titer-blue assays showed an accordant inhibitory effect of UCA1 siRNAs on the cell growth. In conclusion, lncRNA UCA1 might play a substantial role in the occurrence and development of NSCLC, especially in LUAD patients, which is partly due to its effect on caspase-3/7 activity suppression., Competing Interests: None., (IJCEP Copyright © 2018.)

Background: It is generally acknowledged that miRNAs play pivotal roles in the initiation and development of cancer. The aim of the current study is to investigate the clinicopathological role of miR-136-5p in lung adenocarcinoma and its underlying molecular mechanism., Materials and Methods: Data of a cohort of 1242 samples were provided by the Gene Expression Omnibus and The Cancer Genome Atlas to evaluate miR-136-5p expression in lung adenocarcinoma. A comprehensive meta-analysis integrating the expression data from all sources was performed, followed by a summary receiver operating curve plotted to appraise the upregulated expression of miR-136-5p in lung adenocarcinoma. Candidate targets of miR-136-5p were launched by the intersection of differentially expressed genes in The Cancer Genome Atlas and genes predicted by 12 web-based platforms. Then, hub genes were illustrated by a protein-protein interaction network. Furthermore, Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Protein Analysis Through Evolutionary Relationships analyses of potential target genes were carried out via bioinformatics tools., Results: MiR-136-5p expression was upregulated in lung adenocarcinoma versus normal tissues (standard mean difference = 0.43, 95% confidence interval: 0.27-0.58). The summary receiver operating characteristic curve further verified the upregulation of miR-136-5p in lung adenocarcinoma (area under curve = 0.7459). A total of 311 candidate target genes of miR-136-5p were gathered to create a protein-protein interaction network. Molecular mechanism analysis unveiled the potential miR-136-5p target genes participated in cell adhesion molecules, focal adhesion, complement and coagulation cascades and blood coagulation., Conclusion: MiR-136-5p is overexpressed in lung adenocarcinoma and is involved in the molecular mechanism of lung adenocarcinoma via suppressing the expressions of downstream targets, especially claudin-18, sialophorin and syndecan 2 that participate in cell adhesion., (Copyright © 2018. Published by Elsevier GmbH.)

Background: Recent studies have focused on less invasive methods for diagnosing and predicting survival outcomes for colorectal cancer (CRC) patients. Objective: We studied the role of the transcription factor forkhead box P3 (FOXP3) in the tumorigenesis of CRC and investigated its prognostic value in survival outcome estimates. Methods: FOXP3+ regulatory T (Treg) cell levels in CRC and adjacent tissues were measured by immunohistochemistry (IHC) and compared statistically. A literature search was conducted on FOXP3+ Treg cell density and survival rates, including overall survival, disease-free survival, and cancer-specific survival. Meta-analyses were then performed to determine the prognostic value of FOXP3+ Treg cell levels in CRC patients. Results: FOXP3+ Treg cells were increased in CRC tissues over adjacent controls according to the IHC results (t = 14.321; P < 0.001) and cell densities in cases with metastases were higher than those without metastasis (P < 0.05). Cases with serosal infiltration showed higher FOXP3+ Treg cell densities compared to cases without infiltration (P < 0.05) and cell densities in cases differentiated to a lower degree than in cases showing a medium to high degree of differentiation (P < 0.05). Moreover, meta-analysis found a high FOXP3+ Treg cells density in CRC tissues (standardized mean differences = 0.30 [95% CI: 0.03-0.57]), which was correlated with better overall patient survival outcome (hazard ratio = 0.749 [95% CI: 0.648-0.867]). Conclusions: Increased FOXP3+ Treg cells may be an effective marker for tumorigenesis and clinical prognostic evaluation for CRC patients., Competing Interests: None., (IJCEP Copyright © 2018.)

Using the Jintan District of Changzhou City, Jiangsu Province as an example, the LUR model was used to study the spatial distribution of heavy metals and to simulate the spatial distribution of heavy metals in the study area. Compared with the traditional LUR model and the ordinary Kriging interpolation model, the following conclusions were obtained. ① The soil heavy metal content in the study area was highly and significantly correlated with land factors, with the main factor of land use and influencing factors of heavy metals in the soil environment ( P <0.01). In terms of influencing factors, the soil Cu and Zn contents were significantly correlated with the area related to traffic in a 2000 m buffer area and 2000 m buffer zone, respectively. The soil Cr, Cu, and Zn contents were significantly correlated with OM, C org , TC, and TN ( P <0.01). ② The R 2 of the LUR-S models of the spatial distribution of the heavy metals, Pb, Cr, Cu, and Zn, in the study area were improved by 0.041, 0.406, 0.102, and 0.501, respectively, compared with the traditional LUR model. The accuracy test R 2 values were improved by 0.1477, 0.0116, 0.2310, and 0.081, respectively; and the RMSE was reduced by 2.413, 0.631, 1.112, and 2.138, respectively. It was shown that the LUR-S model, which considered the source-sink relationship, had a higher accuracy than the traditional LUR model and ordinary Kriging interpolation model. ③ The LUR-S model was more suitable for the prediction of the spatial distribution of heavy metals with lower pollution and smaller variations, while results for the prediction of the heavy metals with higher pollution and larger variations were worse.

Background: Ubiquitin-conjugating enzyme E2C (UBE2C) has been previously reported to correlate with the malignant progression of various human cancers, however, the exact molecular function of UBE2C in breast carcinoma (BRCA) remained elusive. We aimed to investigate UBE2C expression in BRCA and its clinical significance., Methods: The expression of UBE2C in 209 BRCA tissue samples and 53 adjacent normal tissue samples was detected using immunohistochemistry. The clinical role of UBE2C was analyzed. Public databases including the human protein atlas and Oncomine were used to assess UBE2C expression in BRCA. Moreover, the cancer genome atlas (TCGA) database was employed to investigate the prognostic value of UBE2C in BRCA., Results: The positive expression rate of UBE2C in BRCA was 70.8% (148/209), and UBE2C expression in the adjacent breast tissue was negative. The expression of UBE2C was positively correlated with tumor size (r = 0.32, P < 0.001), histological grade (r = 0.237, P = 0.001), clinical stage (r = 0.198, P = 0.004), lymph node metastasis (r = 0.155, P = 0.026), HER2 expression level (r = 0.356, P < 0.001), Ki-67 expression level (r = 0.504, P < 0.001), and P53 expression level (r = 0.32, P = 0.001). Negative correlations were found between UBE2C expression and the ER (r = - 0.403, P < 0.001) and PR (r = - 0.468, P < 0.001) status. UBE2C gene expression data from the public databases all proved that UBE2C was overexpressed in BRCA. According to the TCGA data analysis, a higher positive expression of UBE2C was associated with worse survival of BRCA patients (P = 0.0428), and data from cBioPortal indicated that 11% of all sequenced BRCA patients possessed a gene alteration of UBE2C, predominately gene amplification and mRNA regulation., Conclusion: Ubiquitin-conjugating enzyme E2C might pose an oncogenic effect on the progression of BRCA.

An extract from a traditional Chinese herb, Marsdeniae tenacissima (trade name, Xiao-Ai-Ping) has been approved for use on the Chinese market as a cancer chemotherapeutic agent for decades. Previous studies have demonstrated the cytostatic and pro-apoptotic effects of M. tenacissima extract (MTE) in multiple cancer cells. However, the contributions of MTE to the proliferation and apoptosis of hepatoma carcinoma cells and the underlying mechanisms remain unclear. In the present study, Bel-7402 cells were incubated with increasing concentrations of MTE ranging from 0-320 µl/ml to explore the effects and potential mechanisms of MTE on the proliferation and apoptosis of Bel-7402 cells. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt and propidium iodide (PI)-stained flow cytometry assays demonstrated that MTE significantly suppressed the proliferation of Bel-7402 cells in a dose-dependent manner by arresting the cell cycle at S phase (P<0.05). Annexin V-fluorescein isothiocyanate PI-stained flow cytometry confirmed the significantly pro-apoptotic effect of MTE at both 160 and 240 µl/ml (P<0.001). Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that MTE (both 160 and 240 µl/ml) induced a significant downregulation of B-cell lymphoma (Bcl)-2 (P<0.01), upregulation of Bcl-2-associated X protein (P<0.01) and activation of caspase-3 (P<0.05). Furthermore, a significant downregulation of murine double minute-2 (MDM2) (P<0.001) and activation of p53 (P<0.001) in Bel-7402 cells following treatment with 160 or 240 µl/ml MTE was observed, accompanied by the inhibition of the nuclear factor (NF)-κB pathway (P<0.001). These results suggested that MTE inhibited growth and exhibited pro-apoptotic effects in Bel-7402 cells, which was mediated by downregulation of the MDM2-induced p53-dependent mitochondrial apoptosis pathway and blocking the NF-κB pathway. Overall, these data serve as preliminary identification of the significant roles of MTE in hepatic carcinoma cells, and suggest that MTE may be a promising candidate for hepatocellular carcinoma therapy.

This comprehensive investigation was performed to evaluate the expression level and potential clinical value of NEAT1 in digestive system malignancies. A total of 57 lncRNA datasets of microarray or RNA-seq and 5 publications were included. The pooled standard mean deviation (SMD) indicated that NEAT1 was down-regulated in esophageal carcinoma (ESCA, SMD = -0.35, 95% CI: -0.5~-0.20, P < 0.0001) and hepatocellular carcinoma (HCC, SMD = -0.47, 95% CI: -0.60~-0.34, P < 0.0001), while in pancreatic cancer (PC), NEAT1 was up-regulated (SMD = 0.45, 95% CI: 0.2~0.71, P = 0.001). However, NEAT1 expression in gastric cancer (GC), colorectal cancer (CRC), biliary tract cancer (BTC) and gallbladder carcinoma (GBC) showed no significant difference between cancer and control groups. The pooled area under the curve values for ESCA, GC, CRC, PC and HCC were 0.60, 0.89, 0.81, 0.77 and 0.69, respectively. Furthermore, our result demonstrated that a high expression of NEAT1 predicted an unfavorable prognosis in patients with digestive system malignancies (HR: 1.50, 95% CI: 1.28-1.76, P < 0.0001). Our study suggests that NEAT1 may play different roles in the initiation and progression of digestive system cancers and could be a potential diagnostic and prognostic biomarker in patients with digestive system carcinomas. Further and stricter studies with a larger number of cases are necessary to strengthen our conclusions.

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L -1 ) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine., (Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: To measure the resting pressure of the tongue body on the sagittal and vertical dimensions of the tongue anchorage pad (TAP), and to investigate the proper position of TAP as an anchorage., Methods: Nineteen volunteers with individual normal occlusion (4 males and 15 females, age 23-33 years) were recruited in the study. Individualized TAP was designed and made for each subject. On the sagittal dimension, the pressure along the midline at the level of the distal of the second premolar (PM2), the first molar (M1) and the second molar (M2) were measured. On the vertical dimension, pressures on TAPs with height of -3 mm, 0 mm, and 3 mm were measured, with 0 mm standing for the reference point recorded by the tongue position record. The tongue resting pressure of the volunteers in the upright position was measured by miniature sensors (FSS1500NS, Honeywell, USA) embedded in TAP. Nonparametric analysis was applied with the significant level of 0.05., Results: On the vertical dimension, the pressure obtained at the height of -3 mm, 0 mm, and 3 mm were 105.83 Pa, 167.75 Pa, and 254.25 Pa, respectively (P<0.001). On the sagittal dimension, the pressure detected at the level of PM2, M1, and M2 were 177.64 Pa, 126.72 Pa, and 109.37 Pa, respectively (P<0.001)., Conclusion: Tongue pressure rises significantly with the increase of TAP height. On the sagittal dimension, pressure decreases along the palatal midline in an anteroposterior direction. But in the clinical practice, we should also put comfort into consideration.

The aim of this study was to fabricate canine bone marrow mesenchymal stem cell sheet through the use of vitamin C, to identify the biological characteristics of the resulting cell sheets, and to reveal the potential mechanism of cell-sheet promotion by vitamin C. This study used vitamin C to induce bone marrow mesenchymal stem cells to proliferate. The resulting cells secreted large amounts of collagen, thereby shortening the construction time of the cell-sheet layer. In addition to these aims, we identified biological microcharacteristics of the cell sheet through histological observation, transmission electron microscopy, real-time PCR detection, immunohistochemical detection, and osteogenesis-induction experiments on the cell sheet. We were able to stably and rapidly construct bone marrow mesenchymal stem cell sheet, effectively harvest it, and transfer the seed cells for tissue engineering. This study indicates that the use of vitamin C for harvesting mesenchymal stem cell sheets from bone marrow may provide an easy and practical approach for bone tissue regeneration., (© Wiley Periodicals, Inc.)

Purpose: To explore the osteogenic mechanism of nonvascular transport distraction osteogenesis (NTDO) by constructing mandibular defects in dogs., Methods: Sixty adult dogs were randomly divided into three groups with 20 dogs in each group. Canine mandibular defect models of NTDO were constructed. Animals were euthanized 1, 4 and 12 weeks after distraction, and the transport disc and surrounding tissue were collected and fixed. Histochemical staining using hematoxylin and eosin (H&E) and electron microscopic observations were used to examine bone regeneration., Results: Distraction bone regeneration was observed in the distraction gap and around the transport disc, and osseous connections had formed between new bone and the transport disc after one week. Osteoclasts gathered around the transport disc, and bone absorption pit formation could be seen. After 4 weeks of distraction, the new bone around the transport disc was close to maturity with thick sclerostin on the middle of the transport disc. After 12 weeks the new bone and the transport disc were fully integrated, and were difficult to distinguish by H&E staining and electron microscopy., Conclusions: Canine mandibular defects were successfully repaired by NTDO resulting in ideal new bone formation and fully recovered mandibular physiological function. The surrounding tissues, including musculoskeletal tissues, the periosteum and other soft tissues and the nonvascular transport disc, together contribute to bone regeneration and neovascularization in NTDO., (Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the expression and significance of Th17 cells and related cytokines in the peripheral blood, skin and lung in a murine model of systemic sclerosis (SSc)., Methods: Twenty female BALB/c mice were randomly divided into 2 groups, including a control group and a bleomycin(BLM) -injected-4-week group (SSc group). Pathological changes of the skin and lung were detected. The proportion of CD4(+)IL-17(+)Th17 cells in the peripheral blood, skin and lung of the mice was determined by flow cytometry. The mRNA expressions of RORγt, IL-17A, and IL-6 of the skin and lung were evaluated by real-time PCR. Enzyme linked immunosorbent assay was used to measure the levels of IL-17 and IL-6 in the serum., Results: Dermal inflammation and the score of PF were significantly increased in the SSc group as compared with the control group (2.60±0.84 vs. 0.40±0.52, 2.80± 1.81 vs.0.60±0.70). Hydroxyproline(HYP) contents of the skin and lung were obviously increased in the SSc group than in the control group [(3.17±1.74) mg/g vs. (1.45±0.40) mg/g,(0.53±0.14) mg/g vs. (0.38±0.16) mg/g], all P<0.05. The percentage of Th17 cells in the peripheral blood, skin and lung of the SSc group were significantly increased as compared with the control group [(2.07±0.89)% vs. (1.02±0.32)%,(5.80±2.02)% vs. (1.64±0.58)%,(5.24±2.43)% vs. (1.92±0.98)%,P <0.01]. Compared with the control group, the mRNA levels of IL-17A, RORγt, IL-6 in the skin and lung of the SSc group were higher. The levels of IL-17, IL-6 of the SSc group in the serum were significantly increased, all P<0.05. The frequency of Th17 cells, and the levels of IL-17 and IL-6 in the blood had a positive correlation with dermal and pulmonary inflammation, fibrosis and HYP contents of the skin and lung, The frequency of Th17, IL-17 and IL-6 in the skin and lung had, respectively, a positive correlation with dermal and pulmonary inflammation, HYP contents of the skin and lung, all P<0.01., Conclusion: Th17 cells were significantly increased in the peripheral blood, skin and lung of a murine model of SSc, and had an intimate relationship with inflammation and fibrosis of the skin and lung, and involved the pathogenesis of SSc through producing IL-17, IL-6.

Objective: To investigate the direct relationship and significance between the pH value of gastric juice and positive fungi in culture critical patients with artificial airway in intensive care unit (ICU) by analyzing and identifying the type of fungi and their sensitivity to antifungal therapy., Methods: A prospective study was conducted.One hundred and sixty patients (between December, 2008 and October, 2011) with artificial airway lasting longer than 48 hours were studied in the ICU at the First Affiliated Hospital of Shenzhen University. The gastric juice specimens were collected through a nasogastric tube, their pH values were measured using precise litmus paper. These samples were divided into six groups according to their pH values: pH ≤ 2.0, pH 2.1-3.0, pH 3.1-4.0, pH 4.1-5.0, pH 5.1-6.0 and pH 6.1-7.0, and then fungi were cultured in these specimens with different pH values. Susceptibility of different fungicide drugs were also investigated. The susceptibility of fungi to gastric juice with different pH values was also investigated. The relationship between 28-day survival rate and the presence of fungi in gastric juice was analyzed in order to analyze the relationship of the presence of fungi in gastric juice and clinical outcome., Results: (1) No fungal growth was found in the gastric juice with pH value lower than 4.0, and the positive rate of fungal culture was significantly increased when the pH value of gastric juice raised. (2) The positive rate of fungal growth was 27.9% (55/197), in which, the positive rate of Candida and non-Candida fungi was 38.2% (21/55) and 61.8% (34/55) respectively, and the difference was significant statistically [χ(2) = 4.16, P < 0.05]. (3) The fungal positive rate was 40.0% (22/55) and 60.0% (33/55) respectively, in survivors (102 cases) and non-survivors (58 cases). The percentage of Candida infection and non-Candida infection was 54.5% (12/22) and 45.5% (10/22) respectively, in survivors, and it was 27.3% (9/33) and 72.7% (24/33), respectively, in non-survivors. The rate of resistance of Candida and non-Candida fungi was 4.7%-14.3% (mean 10.1%) and 0-60% (mean 28.5%) respectively., Conclusions: Positive fungus culture rate was higher in critical patients with artificial airway and higher gastric juice pH values. Non-Candida fungi were mainly found in gastric juice with increasing resistance rate. Candida was more commonly found in survivors, and non-Candida fungi were more commonly found in non-survivors.

Objective: To investigate the effects of fluid resuscitation with different crystalloid-colloid ratio on extravascular lung water (EVLW) in patients with severe acute pancreatitis (SAP)., Methods: Clinical data of 24 SAP patients,who had undergone intrathoracic blood volume index (ITBVI <750 ml/m(2)),were analyzed retrospectively, in Department of Critical Care Medicine in the First Affiliated Hospital of Shenzhen University, during January of 2009 to December of 2010. ITBVI 850-1 000 ml/m(2) was confirmed the end criterion of the end point of resuscitation. Low crystalloid-colloid ratio group (n=13) and high crystalloid-colloid ratio group (n=11) were divided according to crystalloid-colloid ratio (3:1) as the borderline . Hemodynamic parameters, extravascular lung water index (EVLWI), oxygenation index (PaO(2)/FiO(2)), bladder pressure (ICP) and B type natriuretic peptide (BNP) were observed at the time point of before fluid resuscitation, and 0, 24,48, 72 hours after resuscitation, EVLWI was measured with thermal dilution pulse index continuous cardiac output (PiCCO), and BNP with radioimmunoassay., Results: (1)Hemodynamic parameters can be improved at early fluid resuscitation stage in both groups.(2) The total amount of fluid [(16 438±1 758) ml], amount of crystalloid fluid [(13 459±425) ml] and crystalloid-colloid ratio (4.50±0.23) of the high crystalloid-colloid ratio group was significantly higher than that of the low crystalloid-colloid ratio group [(13 895±1 783) ml, (6 945± 454) ml, 2.32±0.18, respectively, P<0.05 or P<0.01] at the time point of 72 hours after resuscitation. (3) Compared with low crystalloid-colloid ratio group, PaO(2)/FiO(2)(mm Hg, 1 mm Hg=0.133 kPa) in high crystalloid-colloid ratio group was lowered significantly at 48 hours and 72 hours after resuscitation (48 hours: 186.51±42.26 vs. 268.35±34.18, 72 hours : 172.85±21.50 vs. 263.95±24.20); but EVLWI, ICP and BNP were increased significantly [EVLWI (ml/kg) 48 hours: 14.52±1.08 vs. 10.40±1.16, 72 hours: 14.92±0.86 vs. 10.52±1.02; ICP (cm H(2)O, 1 cm H(2)O=0.098 kPa) 48 hours: 16.23±1.32 vs. 13.05±1.70, 72 hours: 17.39±1.56 vs. 13.42±1.65; BNP (ng/L) 48 hours: 424.29±74.25 vs. 225.32±53.58, 72 hours: 620.49±79.53 vs. 288.28±68.78, P<0.05 or P<0.01]. (4) The Pearson correlation analysis showed that: EVLWI with PO(2)/FiO(2) was correlated negatively (r=-0.71, P<0.01), but with the BNP, ICP showed positive correlation (r(1)=0.63, r(2)=0.56, both P<0.01)., Conclusion: In order to guide early fluid resuscitation,EVLW, ICP and BNP should be monitored and limited fluid resuscitation strategy with an increasing colloid ratio should be adopted for SAP patients.