Two mutations on S2 subunit were critical for Vero cell tropism expansion of infectious bronchitis virus HV80.

Infectious bronchitis virus (IBV) restricts cell tropism. Except for the Beaudette strain, other IBVs cannot infect mammalian cell lines. The limited cell tropism of other IBVs has hindered IBV vaccine development and research on the mechanisms of IBV infection. A novel Vero cell-adapted strain, HV80, has been previously reported. In this study, we constructed recombinants expressing the chimeric S glycoprotein, S1 or S2 subunit of strain H120 and demonstrated that mutations on S2 subunit are associated with the strain HV80 Vero cell adaptation. R687P or P687R substitution recombinants were constructed with the genome backbone of strains HV80 or H120. We found that the RRRR690/S motif at the S2' cleavage site is crucial to the Vero cell adaptation of strain HV80. Another six amino acid substitutions in the S2 subunit of the recombinants showed that the Q855H mutation induced syncytium formation. A transient transfection assay demonstrated the S glycoprotein with the PRRR690/S motif at the S2' cleavage site induced low-level cell-cell fusion, while H855Q substitution hindered cell-cell fusion and blocked cleavage event with S20 product. This study provides a basis for the construction of IBV recombinants capable of replicating in Vero cells, thus contributing to the advancement in the development of genetically engineered cell-based IBV vaccines.

Downregulation of LHPP Expression Associated with AFP Acts as a Good Prognostic Factor in Human Hepatocellular Carcinoma.

BACKGROUND: Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) serves as a tumor suppressor in hepatocellular carcinoma (HCC), but the correlation between the expression of LHPP and the clinical parameters of oncogenic progression is still not well defined. This study is to reveal the correlation between the expression of LHPP in HCC and their clinical parameters. METHODS: Immunohistochemical analysis was used to assess the correlation between the expression of LHPP and the clinical parameters of HCC. Expressions of LHPP in HCC tissues and cultured HCC cells were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). LHPP, gamma-glutamyl transferase (GGT), and α-fetoprotein (AFP) expression levels in blood or HCC tissues were detected by enzyme-linked immunosorbent assay (ELISA). The Spearman rank correlation coefficient was used to evaluate the correlation of the expression of LHPP and the clinical index of HCC. Correlation of survival and expression of LHPP were analyzed using the Kaplan-Meier method and the log-rank test. RESULTS: Expressions of LHPP in HCC tissues were significantly downregulated than their paired adjacent normal tissues. A significant positive correlation was found between the cytoplasm and nuclear expression of LHPP in both HCC and their paired adjacent normal tissues. The expression of LHPP negatively correlated with the levels of GGT in the cytoplasm of adjacent tissues and with the AFP level in the nucleus of HCC cells. Relative levels of LHPP in HCC tissues were markedly lower than those of the paired adjacent normal tissues. Relative levels of LHPP in LO-2 cells were higher than those of HepG2, BEL-7404, and SMMC-7721 cell lines. The overall survival and DSF survival of patients with the high expression of LHPP were much higher than those with the low expression of LHPP in paired adjacent normal tissue. CONCLUSIONS: LHPP is associated with the AFP level and acts as a good prognostic factor in HCC.

A systematic approach to decode the mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC).

Cornus Officinalis (Cornus), the dried pulp of mature Cornus, is used to treat liver diseases. However, the pharmacological mechanism of Cornus in the treatment of hepatocellular carcinoma (HCC) has not been systematically studied. The chemical compounds and the bioactive chemical compounds of Cornus were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Gene Cards database was used to explore the targets in liver cancer pathogenesis. The disease-drug Venn diagram was constructed using the VENN 2.1 and the STRING database was used to analyze protein-protein Interaction Network (PPI). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R package. Molecular docking was performed using Discovery Studio were assessed using Pymol and Discovery Studio 2016. Cell survival of BEL-7404 cells treated by Hydroxygenkwanin (HGK) were valued through CCK-8 assay. Expressions of caspase-3 and cleaved PARP was detected through Western blot. Pharmacological network diagrams of the Cornus compound-target network and HCC-related target network were successfully constructed. A total of 20 active compounds, 1841 predicted biological targets of Cornus, and 7100 HCC-related targets were identified. 37 target genes between Cornus and HCC were screened trough the network pharmacology. Molecular docking studies suggested that HGK has the highest affinity with caspase-3. HGK could induce apoptosis of HCC cells and significantly activate the caspase-3 protease activity in BEL-7404. This study systematically elaborated the mechanism of Cornus in the treatment of HCC and provided a new perspective to exploit Antineoplastic from Cornus.

Development and Validation of a Nomogram and a Comprehensive Prognostic Analysis of an LncRNA-Associated Competitive Endogenous RNA Network Based on Immune-Related Genes for Locally Advanced Rectal Cancer With Neoadjuvant Therapy.

Colorectal cancer (CRC) is a common digestive tract tumor worldwide. In recent years, neoadjuvant chemoradiotherapy (CRT) has been the most comprehensive treatment for locally advanced rectal cancer (LARC). In this study, we explored immune infiltration in rectal cancer (RC) and identified immune-related differentially expressed genes (IRDEGs). Then, we identified response markers in datasets in GEO databases by principal component analysis (PCA). We also utilized three GEO datasets to identify the up- and downregulated response-related genes simultaneously and then identified genes shared between the PCA markers and three GEO datasets. Based on the hub IRDEGs, we identified target mRNAs and constructed a ceRNA network. Based on the ceRNA network, we explored prognostic biomarkers to develop a prognostic model for RC through Cox regression. We utilized the specimen to validate the expression of the two biomarkers. We also utilized LASSO regression to screen hub IRDEGs and built a nomogram to predict the response of LARC patients to CRT. All of the results show that the nomogram and prognostic model offer good prognostic value and that the ceRNA network can effectively highlight the regulatory relationship. hsa-mir-107 and WDFY3-AS2 may be prognostic biomarkers for RC.

Evaluation of radical surgical treatment in the management of 58 locally advanced rectal neuroendocrine neoplasms, one multicenter retrospective study.

BACKGROUND: Locally advanced rectal neuroendocrine neoplasms (NENs) are rare, and the therapeutic effects of surgery in improving the prognosis have been questioned in previous reports. MATERIALS AND METHODS: The research included 58 consecutive patients with locally advanced rectal NENs from three Chinese medical centers between 2000 and 2020. All have received radical surgical treatment. The clinicopathological and survival data were collected. Kaplan-Meier methods and a Cox proportional hazards regression model were used to evaluate the prognosis and identify independent prognostic factors. RESULTS: All patients were followed up for a median period of 36 (2-125) months. Of the 58 patients, 13 (22.4%) had G1 neuroendocrine tumors (NETs), 15 (25.9%) had G2 NETs, 6 (10.3%) had G3 NETs, and the remaining 24 (41.4%) patients had G3 neuroendocrine carcinomas (NECs). The 1-year and 3-year disease-free survival (DFS) rates were 64.5% and 48.8%, respectively. The 1-year and 3-year overall survival (OS) rates were 90.5% and 75.4%, respectively. Univariate analysis demonstrated that tumor differentiation (p = 0.002), gross morphology (p = 0.009), T stage (p = 0.024), and extramural vascular invasion (p = 0.009) were associated with the OS. The subsequent multivariate analysis confirmed that tumor differentiation [hazard ratio (HR) = 6.002, 95% confidence interval (CI): 1.210-29.767, p = 0.028] and gross morphology (HR = 3.438, 95% CI: 1.038-11.382, p = 0.043) were independent prognostic factors affecting the clinical outcomes. CONCLUSIONS: Rectal NENs are a heterogeneous group of diseases. The survival benefits obtained from surgery vary widely based on the tumor clinicopathological features. Patients with G3 NECs and ulcerative mass are at high risks of poor prognosis.

Differential analysis revealing APOC1 to be a diagnostic and prognostic marker for liver metastases of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most malignant gastrointestinal cancers worldwide. The liver is the most important metastatic target organ, and liver metastasis is the leading cause of death in patients with CRC. Owing to the lack of sensitive biomarkers and unclear molecular mechanism, the occurrence of liver metastases cannot be predicted and the clinical outcomes are bad for liver metastases. Therefore, it is very important to identify the diagnostic or prognostic markers for liver metastases of CRC. AIM: To investigate the highly differentially expressed genes (HDEGs) and prognostic marker for liver metastases of CRC. METHODS: Data from three NCBI Gene Expression Omnibus (GEO) datasets were used to show HDEGs between liver metastases of CRC and tumour or normal samples. These significantly HDEGs of the three GEO datasets take the interactions. And these genes were screened through an online tool to explore the prognostic value. Then, TIMER and R package were utilized to investigate the immunity functions of the HDEGs and gene set enrichment analysis was used to explore their potential functions. RESULTS: Based on the selection criteria, three CRC datasets for exploration (GSE14297, GSE41258, and GSE49355) were chosen. Venn diagrams were used to show HDEGs common to the six groups and 47 HDEGs were obtained. The HDEGs were shown by using STRING and Cytoscape software. Based on the TCGA database, APOC1 showed significantly different expression between N2 and N0, and N2 and N1. And there was also a significant difference in expression between T2 and T4, and between T2 and T3. In 20 paired CRC and normal tissues, quantitative real-time polymerase chain reaction illustrated that the APOC1 mRNA was strongly upregulated in CRC tissues (P = 0.014). PrognoScan and GEPIA2 revealed the prognostic value of APOC1 for overall survival and disease-free survival in CRC (P < 0.05). TIMER showed that APOC1 has a close relationship with immune infiltration (P < 0.05). CONCLUSION: APOC1 is a biomarker that is associated with both the diagnosis and prognosis of liver metastases of CRC.

Identification of genes involved in inbreeding depression of reproduction in Langshan chickens.

OBJECTIVE: Inbreeding depression of reproduction is a major concern in the conservation of native chicken genetic resources. Here, based on the successful development of strongly inbred (Sinb) and weakly inbred (Winb) Langshan chickens, we aimed to evaluate inbreeding effects on reproductive traits and identify candidate genes involved in inbreeding depression of reproduction in Langshan chickens. METHODS: A two-sample t-test was performed to estimate the differences in phenotypic values of reproductive traits between Sinb and Winb chicken groups. Three healthy chickens with reproductive trait values around the group mean values were selected from each of the groups. Differences in ovarian and hypothalamus transcriptomes between the two groups of chickens were analyzed by RNA sequencing (RNA-Seq). RESULTS: The Sinb chicken group showed an obvious inbreeding depression in reproduction, especially for traits of age at the first egg and egg number at 300 days (p<0.01). Furthermore, 68 and 618 differentially expressed genes (DEGs) were obtained in the hypothalamus and ovary between the two chicken groups, respectively. In the hypothalamus, DEGs were mainly enriched in the pathways related to vitamin metabolism, signal transduction and development of the reproductive system, such as the riboflavin metabolism, Wnt signaling pathway, extracellular matrix-receptor interaction and focal adhesion pathways, including stimulated by retinoic acid 6, serpin family F member 1, secreted frizzled related protein 2, Wnt family member 6, and frizzled class receptor 4 genes. In the ovary, DEGs were significantly enriched in pathways associated with basic metabolism, including amino acid metabolism, oxidative phosphorylation, and glycosaminoglycan degradation. A series of key DEGs involved in folate biosynthesis (gamma-glutamyl hydrolase, guanosine triphosphate cyclohydrolase 1), oocyte meiosis and ovarian function (cytoplasmic polyadenylation element binding protein 1, structural maintenance of chromosomes 1B, and speedy/RINGO cell cycle regulator family member A), spermatogenesis and male fertility (prostaglandin D2 synthase 21 kDa), Mov10 RISC complex RNA helicase like 1, and deuterosome assembly protein 1) were identified, and these may play important roles in inbreeding depression in reproduction. CONCLUSION: The results improve our understanding of the regulatory mechanisms underlying inbreeding depression in chicken reproduction and provide a theoretical basis for the conservation of species resources.

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy.

BACKGROUND: Colorectal cancer is a common digestive cancer worldwide. As a comprehensive treatment for locally advanced rectal cancer (LARC), neoadjuvant therapy (NT) has been increasingly used as the standard treatment for clinical stage II/III rectal cancer. However, few patients achieve a complete pathological response, and most patients require surgical resection and adjuvant therapy. Therefore, identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance. AIM: To establish effective prognostic nomograms and risk score prediction models to predict overall survival (OS) and disease-free survival (DFS) for LARC treated with NT. METHODS: Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017. The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors, which were validated by the Cox regression method. Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves, and that of the two nomograms was conducted by calculating the concordance index (C-index) and calibration curves. The results were validated in a cohort of 65 patients from 2015 to 2017. RESULTS: Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model: Vascular_tumors_bolt, cancer nodules, yN, body mass index, matchmouth distance from the edge, nerve aggression and postoperative carcinoembryonic antigen. The nomogram showed good predictive value for OS, with a C-index of 0.91 (95%CI: 0.85, 0.97) and good calibration. In the validation cohort, the C-index was 0.69 (95%CI: 0.53, 0.84). The risk factor prediction model showed good predictive value. The areas under the curve for 3- and 5-year survival were 0.811 and 0.782. The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77 (95%CI: 0.69, 0.85). In the validation cohort, the C-index was 0.71 (95%CI: 0.61, 0.81). The prediction model for DFS also had good predictive value, with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754. CONCLUSION: We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.

Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

Colorectal cancer (CRC) is a common malignant tumor of the digestive tract and lacks specific diagnostic markers. In this study, we utilized 10 public datasets from the NCBI Gene Expression Omnibus (NCBI-GEO) database to identify a set of significantly differentially expressed genes (DEGs) between tumor and control samples and WGCNA (Weighted Gene Co-Expression Network Analysis) to construct gene co-expression networks incorporating the DEGs from The Cancer Genome Atlas (TCGA) and then identify genes shared between the GEO datasets and key modules. Then, these genes were screened via MCC to identify 20 hub genes. We utilized regression analyses to develop a prognostic model and utilized the random forest method to validate. All hub genes had good diagnostic value for CRC, but only CLCA1 was related to prognosis. Thus, we explored the potential biological value of CLCA1. The results of gene set enrichment analysis (GSEA) and immune infiltration analysis showed that CLCA1 was closely related to tumor metabolism and immune invasion of CRC. These analysis results revealed that CLCA1 may be a candidate diagnostic and prognostic biomarker for CRC.

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients.

BACKGROUND: Epidemiologically, in China, locally advanced rectal cancer is a more common form of rectal cancer. Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival (DFS) and pathologic response after surgery. At present, this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers, but the optimal time for surgery after neoadjuvant therapy is still controversial. AIM: To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer. METHODS: A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study. The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery: 139 (60.2%) patients were in group A (≤ 9 wk), and 92 (39.2%) patients were in group B (> 9 wk). DFS and pathologic response were analyzed as the primary endpoints. The secondary endpoints were postoperative complications and sphincter preservation. RESULTS: For the 231 patients included, surgery was performed at ≤ 9 wk in 139 (60.2%) patients and at > 9 wk in 92 (39.8%). The patients' clinical characteristics, surgical results, and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis. The overall pathologic complete response (pCR) rate was 27.2% (n = 25) in the longer time interval group (> 9 wk) and 10.8% (n = 15) in the shorter time interval group (≤ 9 wk, P = 0.001). The postoperative complications did not differ between the groups (group A, 5% vs group B, 5.4%; P = 0.894). Surgical procedures for sphincter preservation were performed in 113 (48.9%) patients, which were not significantly different between the groups (group A, 52.5% vs group B, 43.5%; P = 0.179). The pCR rate was an independent factor affected by time interval (P = 0.009; odds ratio [OR] = 2.668; 95%CI: 1.276-5.578). Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval (> 9 wk) was a significant independent prognostic factor for DFS (P = 0.032; OR = 2.295; 95%CI: 1.074-4.905), but the time interval was not an independent prognostic factor for overall survival (P > 0.05). CONCLUSION: A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.

MIR17HG polymorphism (rs7318578) is associated with liver cancer risk in the Chinese Han population.

Numerous evidence has revealed that single-nucleotide polymorphisms (SNPs) are associated with liver cancer risk. To assess whether the MIR17HG polymorphisms are associated with the liver cancer risk in the Chinese Han population, we performed a case-control (432 liver cancer patients and 430 healthy controls) study. Genotyping of four variants of MIR17HG was performed with the Agena MassARRAY platform. We used χ2 test to compare the distribution of SNPs allele and genotypes frequencies of cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis to evaluate the association under genetic models. The results indicated that the rs7318578 was significantly associated with increased the risk of liver cancer in the allele (OR = 1.45, 95% CI: 1.18-1.77, P=3.04E-04), recessive (OR = 3.69, 95% CI: 2.45-5.56, P=4.52E-10) and additive model (OR = 1.35, 95% CI: 1.13-1.62, P=0.001). Moreover, we found that individuals with the genotype CC of rs7318578 presented with an increased risk of liver cancer (OR = 3.03, 95% CI: 1.98-4.65, P=3.83E-07); however, the CA genotype of rs7318578 significantly decreased the risk of liver cancer (OR = 0.61, 95% CI: 0.45-0.83, P=0.001, compared with those with the AA genotype. Our findings indicated that MIR17HG polymorphism (rs7318578) contributes to liver cancer susceptibility to the Chinese Han population. Further studies with larger samples are required to confirm the results, as well as functional studies to determine the role of this SNP in miRNA expression or molecular pathways.

Low ligation has a lower anastomotic leakage rate after rectal cancer surgery.

BACKGROUND: For laparoscopic rectal cancer surgery, the inferior mesenteric artery (IMA) can be ligated at its origin from the aorta [high ligation (HL)] or distally to the origin of the left colic artery [low ligation (LL)]. Whether different ligation levels are related to different postoperative complications, operation time, and lymph node yield remains controversial. Therefore, we designed this study to determine the effects of different ligation levels in rectal cancer surgery. AIM: To investigate the operative results following HL and LL of the IMA in rectal cancer patients. METHODS: From January 2017 to July 2019, this retrospective cohort study collected information from 462 consecutive rectal cancer patients. According to the ligation level, 235 patients were assigned to the HL group while 227 patients were assigned to the LL group. Data regarding the clinical characteristics, surgical characteristics and complications, pathological outcomes and postoperative recovery were obtained and compared between the two groups. A multivariate logistic regression analysis was performed to evaluate the possible risk factors for anastomotic leakage (AL). RESULTS: Compared to the HL group, the LL group had a significantly lower AL rate, with 6 (2.8%) cases in the LL group and 24 (11.0%) cases in the HL group (P = 0.001). The HL group also had a higher diverting stoma rate (16.5% vs 7.5%, P = 0.003). A multivariate logistic regression analysis was subsequently performed to adjust for the confounding factors and confirmed that HL (OR = 3.599; 95%CI: 1.374-9.425; P = 0.009), tumor located below the peritoneal reflection (OR = 2.751; 95%CI: 0.772-3.985; P = 0.031) and age (≥ 65 years) (OR = 2.494; 95%CI: 1.080-5.760; P = 0.032) were risk factors for AL. There were no differences in terms of patient demographics, pathological outcomes, lymph nodes harvested, blood loss, hospital stay and urinary function (P > 0.05). CONCLUSION: In rectal cancer surgery, LL should be the preferred method, as it has a lower AL and diverting stoma rate.

Selective lateral lymph node dissection after neoadjuvant chemoradiotherapy in rectal cancer.

BACKGROUND: Lateral lymph node metastasis is one of the leading causes of local recurrence in patients with advanced mid or low rectal cancer. Neoadjuvant chemoradiotherapy (NCRT) can effectively reduce the postoperative recurrence rate; thus, NCRT with total mesorectal excision (TME) is the most widely accepted standard of care for rectal cancer. The addition of lateral lymph node dissection (LLND) after NCRT remains a controversial topic. AIM: To investigate the surgical outcomes of TME plus LLND, and the possible risk factors for lateral lymph node metastasis after NCRT. METHODS: This retrospective study reviewed 89 consecutive patients with clinical stage II-III mid or low rectal cancer who underwent TME and LLND from June 2016 to October 2018. In the NCRT group, TME plus LLND was performed in patients with short axis (SA) of the lateral lymph node greater than 5 mm. In the non-NCRT group, TME plus LLND was performed in patients with SA of the lateral lymph node greater than 10 mm. Data regarding patient demographics, clinical workup, surgical procedure, complications, and outcomes were collected. Multivariate logistic regression analysis was performed to evaluate the possible risk factors for lateral lymph node metastasis in NCRT patients. RESULTS: LLN metastasis was pathologically confirmed in 35 patients (39.3%): 26 (41.3%) in the NCRT group and 9 (34.6%) in the non-NCRT group. The most common site of metastasis was around the obturator nerve (21/35) followed by the internal iliac artery region (12/35). In the NCRT patients, 46% of patients with SA of LLN greater than 7 mm were positive. The postoperative 30-d mortality rate was 0%. Two (2.2%) patients suffered from lateral local recurrence in the 2-year follow up. Multivariate analysis showed that cT4 stage (odds ratio [OR] = 5.124, 95% confidence interval [CI]: 1.419-18.508; P = 0.013), poor differentiation type (OR = 4.014, 95%CI: 1.038-15.520; P = 0.044), and SA ≥ 7 mm (OR = 7.539, 95%CI: 1.487-38.214; P = 0.015) were statistically significant risk factors associated with LLN metastasis. CONCLUSION: NCRT is not sufficient as a stand-alone therapy to eradicate LLN metastasis in lower rectal cancer patients and surgeons should consider performing selective LLND in patients with greater LLN SA diameter, poorer histological differentiation, or advanced T stage. Selective LLND for NCRT patients can have a favorable oncological outcome.

MiRNA155HG polymorphisms influenced the risk of liver cancer among the Han Chinese population.

BACKGROUND: Liver cancer is one of the most common cancers in the world. The primary aim of this research was to discover the correlation between single nucleotide polymorphisms (SNPs) of the MIR155HG and liver cancer risk. METHODS: The selected SNPs in MIR155HG were genotyped utilizing the Agena MassARRAY platform. We evaluated the correlation between MIR155HG polymorphisms and Liver cancer by genetic model analysis, stratification analysis and haplotype analysis. Relative risk of Liver cancer was shown based on odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Our results uncovered that rs12482371 and rs1893650 in the MIR155HG were associated with protection against Liver cancer. And the rs928883 was related to increase risk of Liver cancer. Furthermore, apart from rs77218221, other selected SNPs formed two LD blocks, and haplotype "GATAG" in block 2 elevated individual liver cancer risk. CONCLUSIONS: MIR155HG gene polymorphism may be correlated to Liver cancer susceptibility in Han Chinese population, particularly in males and aged ≤55 years.

Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1.

Interleukin-34 (IL-34) is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colony-stimulating factor-1 receptor (CSF-1R). However, information on the function of IL-34 in fish remains limited. In the present study, we identified an IL-34 homolog from mudskippers ( Boleophthalmus pectinirostris). In silico analysis showed that the mudskipper IL-34 (BpIL-34) was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper ( Epinephelus coioides) homolog. BpIL-34 transcripts were constitutively expressed in various tissues, with the highest level of expression found in the brain. Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues. The recombinant mature BpIL-34 peptide (rBpIL-34) was purified and used to produce anti-rBpIL-34 IgG. Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages (MOs/MФs) was N-glycosylated. In vitro, rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs, as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factor α ( BpTNF-α) and BpIL-1ß in these cells. Furthermore, the knockdown of mudskipper CSF-1R1 ( BpCSF-1R1), but not mudskipper BpCSF-1R2, significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФ function. In conclusion, our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

Corrigendum: Differential Expression Analysis Revealing CLCA1 to Be a Prognostic and Diagnostic Biomarker for Colorectal Cancer.

[This corrects the article DOI: 10.3389/fonc.2020.573295.].

Impact factors of lymph node retrieval on survival in locally advanced rectal cancer with neoadjuvant therapy.

BACKGROUND: Conventional clinical guidelines recommend that at least 12 lymph nodes should be removed during radical rectal cancer surgery to achieve accurate staging. The current application of neoadjuvant therapy has changed the number of lymph node dissection. AIM: To investigate factors affecting the number of lymph nodes dissected after neoadjuvant chemoradiotherapy in locally advanced rectal cancer and to evaluate the relationship of the total number of retrieved lymph nodes (TLN) with disease-free survival (DFS) and overall survival (OS). METHODS: A total of 231 patients with locally advanced rectal cancer from 2015 to 2017 were included in this study. According to the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification system and the NCCN guidelines for rectal cancer, the patients were divided into two groups: group A (TLN ≥ 12, n = 177) and group B (TLN < 12, n = 54). Factors influencing lymph node retrieval were analyzed by univariate and binary logistic regression analysis. DFS and OS were evaluated by Kaplan-Meier curves and Cox regression models. RESULTS: The median number of lymph nodes dissected was 18 (range, 12-45) in group A and 8 (range, 2-11) in group B. The lymph node ratio (number of positive lymph nodes/total number of lymph nodes) (P = 0.039) and the interval between neoadjuvant therapy and radical surgery (P = 0.002) were independent factors of the TLN. However,TLN was not associated with sex, age, ASA score, clinical T or N stage, pathological T stage, tumor response grade (Dworak), downstaging, pathological complete response, radiotherapy dose, preoperative concurrent chemotherapy regimen, tumor distance from anal verge, multivisceral resection, preoperative carcinoembryonic antigen level, perineural invasion, intravascular tumor embolus or degree of differentiation. The pathological T stage (P < 0.001) and TLN (P < 0.001) were independent factors of DFS, and pathological T stage (P = 0.011) and perineural invasion (P = 0.002) were independent factors of OS. In addition, the risk of distant recurrence was greater for TLN < 12 (P = 0.009). CONCLUSION: A shorter interval to surgery after neoadjuvant chemoradiotherapy for rectal cancer under indications may cause increased number of lymph nodes harvested. Tumor shrinkage and more extensive lymph node retrieval may lead to a more favorable prognosis.

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals.

BACKGROUND: Colorectal high-grade neuroendocrine neoplasms (HGNENs) are rare and constitute less than 1% of all colorectal malignancies. Based on their morphological differentiation and proliferation identity, these neoplasms present heterogeneous clinicopathologic features. Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial. AIM: To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy. METHODS: This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019. The clinicopathologic characteristics and follow-up data were carefully collected from their medical records, outpatient reexaminations, and telephone interviews. A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease. RESULTS: According to the latest recommendations for the classification and nomenclature of colorectal HGNENs, 61 (84.7%) patients in our cohort had poorly differentiated neoplasms, which were categorized as high-grade neuroendocrine carcinomas (HGNECs), and the remaining 11 (15.3%) patients had well differentiated neoplasms, which were categorized as high-grade neuroendocrine tumors (HGNETs). Most of the neoplasms (63.9%) were located at the rectum. More than half of the patients (51.4%) presented with distant metastasis at the date of diagnosis. All patients were followed for a median duration of 15.5 mo. In the entire cohort, the median survival time was 31 mo, and the 3-year and 5-year survival rates were 44.3% and 36.3%, respectively. Both the univariate and multivariate analyses demonstrated that increasing age, HGNEC type, and distant metastasis were risk factors for poor clinical outcomes. CONCLUSION: Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes. However, patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.

Intraoperative intraperitoneal chemotherapy increases the incidence of anastomotic leakage after anterior resection of rectal tumors.

BACKGROUND: Intraoperative intraperitoneal chemotherapy is an emerging treatment modality for locally advanced rectal neoplasms. However, its impacts on postoperative complications remain unknown. Anastomotic leakage (AL) is one of the most common and serious complications associated with the anterior resection of rectal tumors. Therefore, we designed this study to determine the effects of intraoperative intraperitoneal chemotherapy on AL. AIM: To investigate whether intraoperative intraperitoneal chemotherapy increases the incidence of AL after the anterior resection of rectal neoplasms. METHODS: This retrospective cohort study collected information from 477 consecutive patients who underwent an anterior resection of rectal carcinoma using the double stapling technique at our institution from September 2016 to September 2017. Based on the administration of intraoperative intraperitoneal chemotherapy or not, the patients were divided into a chemotherapy group (171 cases with intraperitoneal implantation of chemotherapy agents during the operation) or a control group (306 cases without intraoperative intraperitoneal chemotherapy). Clinicopathologic features, intraoperative treatment, and postoperative complications were recorded and analyzed to determine the effects of intraoperative intraperitoneal chemotherapy on the incidence of AL. The clinical outcomes of the two groups were also compared through survival analysis. RESULTS: The univariate analysis showed a significantly higher incidence of AL in the patients who received intraoperative intraperitoneal chemotherapy, with 13 (7.6%) cases in the chemotherapy group and 5 (1.6%) cases in the control group (P = 0.001). As for the severity of AL, the AL patients who underwent intraoperative intraperitoneal chemotherapy tended to be more severe cases, and 12 (92.3%) out of 13 AL patients in the chemotherapy group and 2 (40.0%) out of 5 AL patients in the control group required a secondary operation (P = 0.044). A multivariate analysis was subsequently performed to adjust for the confounding factors and also showed that intraoperative intraperitoneal chemotherapy increased the incidence of AL (odds ratio = 5.386; 95%CI: 1.808-16.042; P = 0.002). However, the survival analysis demonstrated that intraoperative intraperitoneal chemotherapy could also improve the disease-free survival rates for patients with locally advanced rectal cancer. CONCLUSION: Intraoperative intraperitoneal chemotherapy can improve the prognosis of patients with locally advanced rectal carcinoma, but it also increases the risk of AL following the anterior resection of rectal neoplasms.