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Background: Intestinal fistula is one of the common complications of Crohn's disease (CD) that might require surgical treatment. The clinical characteristics and outcomes of CD with intestinal fistula are much different from CD alone. This study was to investigate whether the coagulation status of CD is changed by intestinal fistula. Methods: Data were retrospectively analyzed for 190 patients with a definitive diagnosis of CD who were registered at the Jinling Hospital between January 2014 and September 2015. Baseline clinical characteristics and laboratory indices of initial admission and 7 days after intestinal fistula resections were collected. Student's t-test and the Wilcoxon rank-sum test were used to compare differences between the two groups. Results: Compared with CD patients without intestinal fistula, prothrombin time (PT) in patients with intestinal fistula was significantly longer (12.13 ± 1.27 s vs. 13.18 ± 1.51 s, P < 0.001 in overall cohort; 11.56 ± 1.21 s vs. 12.61 ± 0.73 s, P = 0.001 in females; and 12.51 ± 1.17 s vs. 13.37 ± 1.66 s, P = 0.003 in males). Platelet (PLT) count was much lower in intestinal fistula group than in nonintestinal fistula group (262.53 ± 94.36 × 109/L vs. 310.36 ± 131.91 × 109/L, P = 0.009). Multivariate logistic regression showed that intestinal fistula was significantly associated with a prolonged PT (odds ratio [OR] = 1.900, P < 0.001), a reduced amount of PLT (OR = 0.996, P = 0.024), and an increased operation history (OR = 5.408, P < 0.001). Among 65 CD patients receiving intestinal fistula resections, PT was obviously shorter after operation than baseline (12.28 ± 1.16 s vs. 13.02 ± 1.64 s, P = 0.006). Conclusions: Intestinal fistula was significantly associated with impaired coagulation status in patients complicated with CD. Coagulation status could be improved after intestinal fistula resections.

Background: Increasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice. Methods: An article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: “Fusobacterium nucleatum”, ”Fusobacterium spp.”, ”Fn”, “colorectal cancer(s)”, “colorectal carcinoma(s)”, “colorectal neoplasm(s)”, and “colorectal tumor(s)”. Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized. Results: Finally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83–0.89), the pooled sensitivity: 0.81 (95% CI: 0.64–0.91), specificity: 0.77 (95% CI: 0.59–0.89), and DOR: 14.00 (95% CI: 9.00–22.00). Conclusion: Intestinal F. nucleatum is a valuable marker for CRC diagnosis.

Background: Wide resection margins of osseous tumors are associated with a low incidence of local recurrence, making accurate measurement of the intraosseous extent of primary malignant long bone tumors is crucial. We compared the intraosseous tumor extent assessed by magnetic resonance imaging (MRI) with the gross specimen to evaluate the accuracy of MRI. Methods: A total of 255 patients with primary malignant tumors in the long bones were included. Using MRI, we defined the length of tumor as the distance from the articular surface to the boundary between abnormal and normal marrow signal. The extent of the abnormal intraosseous signal was measured on unenhanced T1-weighted (T1WI) magnetic resonance images after chemotherapy. All gross surgical specimens were sectioned, and tumor extent was measured. Wilcoxon signed-rank test was used to test the differences between MRI and gross specimen findings. Spearman's correlation analysis was used to test the correlation between groups. Results: Median tumor length by gross specimen (112 mm; range, 45–300 mm) was longer than that by MRI (108 mm; range, 45–304 mm; Z = −6.916, P < 0.001). Of 255 images, tumor length was accurately represented on 27 T1WI magnetic resonance images, overestimated on 79 images, and underestimated on 149 images. The median difference between imaging and gross specimen measurements was 2.0 mm (range: 1.0–15.0 mm) for the 79 cases where tumor length was overestimated, and 5.0 mm (range: 1.0–18.0 mm) for the 149 cases where tumor length was underestimated. The Spearman correlation demonstrated a high correlation of tumor length on gross specimen with the tumor length on MRI (R = 0.99, P < 0.01). Conclusions: We conclude that preoperative MRI could be a useful method in determining intramedullary malignant bone tumor boundaries and may serve as an accepted assessment method of long bone tumors before limb-sparing surgery.

Background: Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case–control studies. Methods: PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle–Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score. Results: A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35–2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of

Background: Human U three protein 14a (hUTP14a) promotes p53 degradation. Moreover, hUTP14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP14a in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate hUTP14a expression and its prognostic value in HCC. Methods: The hUTP14a expression was evaluated using immunohistochemistry (IHC) in HCC tissue specimens. The correlations between hUTP14a expression and clinicopathological variables were analyzed. The Kaplan-Meier method was used to analyze the association between hUTP14a expression and survival. Independent prognostic factors associated with overall survival (OS) and disease-free survival (DFS) were analyzed using the Cox proportional-hazards regression model. Results: The IHC data revealed that the hUTP14a positivity rate in HCC tissue specimens was significantly higher than that in nontumorous tissue specimens (89.9% vs. 72.7%, P < 0.05). The hUTP14a expression was detected in both the nucleolus and the cytoplasm. The positivity rate of nucleolar hUTP14a expression in HCC tissue specimens was higher than that in the nontumorous tissue specimens (29.3% vs. 10.1%, P < 0.05). No significant difference was found between HCC and nontumorous tissue specimens of cytoplasmic hUTP14a expression (60.6% vs. 62.6%, P > 0.05). In addition, no significant correlation was found between nucleolar hUTP14a expression and other clinicopathological variables. The 5-year OS and DFS rates in patients with positive nucleolar hUTP14a expression were significantly lower than those in patients with negative hUTP14a expression (P = 0.004 for OS, P = 0.003 for DFS). Multivariate analysis showed that nucleolar hUTP14a expression was an independent prognostic factor for OS (P = 0.004) and DFS (P < 0.001). Conclusions: The positivity rate of hUTP14a expression was significantly higher in HCC specimens. Positive expression of nucleolar hUTP14a might act as a novel prognostic predictor for patients with HCC.

Background: Chronic intermittent hypoxia is the most remarkable feature of obstructive sleep apnea/hypopnea syndrome and it can induce the change of hypoxia-inducible factor-1α (HIF-1α) expression and contractile properties in the genioglossus. To clarify the role of HIF-1α in contractile properties of the genioglossus, this study generated and compared high-throughput RNA-sequencing data from genioglossus between HIF-1α conditional knockout (KO) mice and littermate wild-type (WT) mice. Methods: KO mice were generated with cre-loxP strategy. Gene expression profile analysis was performed using gene enrichment analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differently expressed messenger RNAs were performed to identify the related pathways and biological functions. Six differentially expressed genes (DEGs) were validated by qualitative reverse transcription polymerase chain reaction. Results: A total of 142 (77 upregulated and 65 downregulated) transcripts were found to exhibit statistically significant difference between the HIF-1α-KO and WT mice. GO and KEGG analyses indicated that DEGs included genes involved in “skeletal muscle cell differentiation,” “muscle organ development,” “glucose metabolic process,” “glycogen biosynthetic and metabolic process,” etc. Conclusion: This study might provide evidence that HIF-1α affects the expression of multiple genes involved in the myogenesis, muscle development, and carbohydrate metabolism through transcriptome analysis in conditional HIF-1α-KO mice.

Background: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. This study was conducted to examine whether the association of a proliferation-inducing ligand (APRIL), spermatogenesis associated 8 (SPATA8), platelet-derived growth factor receptor-alpha (PDGFRA), and DNA polymerase beta (POLB) with SLE can be replicated in a Chinese Han population. Methods: Chinese SLE patients (n = 1247) and ethnically and geographically matched healthy controls (n = 1440) were genotyped for the APRIL, SPATA8, PDGFRA, and POLB single-nucleotide polymorphisms (SNPs), rs3803800, rs8023715, rs1364989, and rs12678588 using the Sequenom MassARRAY System. Results: The Chinese Han SLE patients and controls had statistically similar frequencies of alleles and genotypes of four gene polymorphisms. Moreover, no association signal was detected on different genetic models (additive, dominant, and recessive, all, P> 0.05) or in SLE subgroups stratified by various clinical manifestations (all, P> 0.05). Conclusions: Different genetic backgrounds from different ancestries and various populations may result in different genetic risk factors for SLE. We did not detect any significant association with SNPs of APRIL, SPATA8, PDGFRA, and POLB.

Background: Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma. Methods: Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995–2014), the American Society of Clinical Oncology (1995–2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings “MM “ and “thalidomide “. Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings. Results: Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72–0.94) for overall survival (OS), and 0.65 (95% CI: 0.58–0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24–5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43–5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95–1.63], P = 0.120). Conclusion: Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.

Background: For a child with osteosarcoma, prediction of the limb length discrepancy at maturity is important when planning for limb salvage surgery. The purpose of this study was to provide a reliable prediction method. Methods: A retrospective review of Chinese children receiving chemotherapy for osteosarcoma before skeletal maturity was conducted. Standing full-length radiographs of the lower extremity were used for length measurements. Length-for-age curves were constructed using the LMS method. The lower limb multiplier for a specific age and gender was calculated using the formula M = Lm/L, where M was the gender- and age-specific multiplier, Lmwas the bone length at maturity, and L was the age-specific bone length. Prematurity and postmaturity radiographs were used to assess the accuracy of the prediction methods. Results: A total of 513 radiographs of 131 boys and 314 radiographs of 86 girls were used to calculate the coefficients of the multiplier. The multipliers of 8-, 9-, 10-, 11-, 12-, 13-, 14-, 15-, 16-, 17-, and 18-year-old boys after chemotherapy for osteosarcoma were 1.394, 1.306, 1.231, 1.170, 1.119, 1.071, 1.032, 1.010, 1.004, 1.001, and 1.000, respectively; while for girls at the same ages, the multipliers were 1.311, 1.221, 1.146, 1.092, 1.049, 1.021, 1.006, 1.001, 1.000, 1.000, and 1.000, respectively. Prematurity and postmaturity femoral and tibial lengths of 21 patients were used to assess the prediction accuracy. The mean prediction error was 0 cm, 0.8 cm, and 1.6 cm for the multiplier method using our coefficients, Paley's coefficients, and Anderson's method, respectively. Conclusions: Our coefficients for the multiplier method are reliable in predicting lower limb length growth of Chinese children with osteosarcoma.

Background: Pyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear. Methods: C57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence. Results: The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS. Conclusions: This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.

Background: Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients. Methods: This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic. Results: The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7 th (TNM 7 th ) (AIC = 2899.980), TNM 6 th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389). Conclusions: BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

Background: DNA hypomethylation of long interspersed nuclear elements-1 (LINEs-1) occurs during carcinogenesis, whereas information addressing LINE-1 methylation in Wilms tumor (WT) is limited. The main purpose of our study was to quantify LINE-1 methylation levels and evaluate their relationship with relative telomere length (TL) in WT. Methods: We investigated LINE-1 methylation and relative TL using bisulfite-polymerase chain reaction (PCR) pyrosequencing and quantitative PCR, respectively, in 20 WT tissues, 10 normal kidney tissues and a WT cell line. Significant changes were analyzed by t-tests. Results: LINE-1 methylation levels were significantly lower (P < 0.05) and relative TLs were significantly shorter (P < 0.05) in WT compared with normal kidney. There was a significant positive relationship between LINE-1 methylation and relative TL in WT (r = 0.671, P = 0.001). LINE-1 Methylation levels were significantly associated with global DNA methylation (r = 0.332, P < 0.01). In addition, relative TL was shortened and LINE-1 methylation was decreased in a WT cell line treated with the hypomethylating agent 5-aza-2′-deoxycytidine compared with untreated WT cell line. Conclusion: These results suggest that LINE-1 hypomethylation is common and may be linked to telomere shortening in WT.

Background: This study characterized the cardiac telocyte (TC) population both in vivo and in vitro, and investigated its telomerase activity related to mitosis. Methods: Using transmission electron microscopy and a phase contrast microscope, the typical morphological features of cardiac TCs were observed; by targeting the cell surface proteins CD117 and CD34, CD117 + CD34 + cardiac TCs were sorted via flow cytometry and validated by immunofluorescence based on the primary cell culture. Then the optimized basal nutrient medium for selected population was examined with the cell counting kit 8. Under this conditioned medium, the process of cell division was captured, and the telomerase activity of CD117 + CD34 + cardiac TCs was detected in comparison with bone mesenchymal stem cells (BMSCs), cardiac fibroblasts (CFBs), cardiomyocytes (CMs). Results: Cardiac TCs projected characteristic telopodes with thin segments (podomers) in alternation with dilation (podoms). In addition, 64% of the primary cultured cardiac TCs were composed of CD117 + CD34 + cardiac TCs; which was verified by immunofluorescence. In a live cell imaging system, CD117 + CD34 + cardiac TCs were observed to enter into cell division in a short time, followed by an significant invagination forming across the middle of the cell body. Using a real-time quantitative telomeric-repeat amplification assay, the telomerase concentration in CD117 + CD34 + cardiac TCs was obviously lower than in BMSCs and CFBs, and significantly higher than in CMs. Conclusions: Cardiac TCs represent a unique cell population and CD117 + CD34 + cardiac TCs have relative low telomerase activity that differs from BMSCs, CFBs and CMs and thus they might play an important role in maintaining cardiac homeostasis.