Search

Background Adenocarcinoma of esophagogastric junction (AEG) is a high-mortality gastrointestinal cancer lacking effective prognostic markers. Pyroptosis, a form of programmed cell death, is vital in inflammation and immune response. However, the prognostic role of pyroptosis-related lncRNA in AEG has not been explored.Methods Clinical information and gene expression data for AEG were obtained from The Cancer Genome Atlas (TCGA). The least absolute shrinkage and selection operator (LASSO) was used to narrow down candidate lncRNAs and develop the pyroptosis-related lncRNA risk model. Kaplan-Meier analysis, Multivariate Cox regression, and nomogram were used to assess the risk model. Functional enrichment analysis was used to reveal potential pathways in AEG. The ESTIMATE, TIMER, XCELL, CIBERSORT, ssGSEA, and EPIC algorithms were used to investigate the immune status in different risk groups. The oncoPredict R package was used to identify candidate drugs.Results Pearson correlation analysis identified 816 pyroptosis-related lncRNAs, from which three prognostic lncRNAs (LINC01537, CTD-2033D15.2, ENTPD1-AS1) were selected to construct a risk model using LASSO Cox regression analysis. Kaplan-Meier curve analysis revealed that patients with low-risk scores had superior overall survival (OS) compared to those in the high-risk groups (HR = 1.86, 95% CI 1.21–2.87, p = 0.004). Multivariate analysis demonstrated that the 3 prognostic lncRNA risk score was an independent prognostic factor with a significant predictive value for AEG. A low-risk score indicated an increased infiltration of activated memory CD4 + T cells and was associated with pathways such as DNA replication, cell cycle, mismatch repair, aminoacyl-tRNA biosynthesis, and seleno amino acid metabolism. Additionally, a low-risk score was associated with increased sensitivity to Paclitaxel and KRAS (G12C) inhibitor drugs.Conclusion These results provide new insights into the potential use of the proposed pyroptosis-related lncRNA signature as a prognostic tool and potential therapeutic targets for AEG.

Accumulating evidence suggests that cellular senescence promotes tumor formation and that long non-coding RNAs (lncRNAs) expression predicts tumor prognosis. However, senescence-related variables, particularly lncRNAs, are still largely unknown. Therefore, the present study developed a novel senescence-associated lncRNA signature to predict colorectal cancer (CRC) prognosis.A co-expression network of senescence-associated mRNAs and lncRNAs was built using RNA-sequence data from The Cancer Genome Atlas (TCGA). By using the prognosis outcomes data of overall survival (OS) and disease-free survival (DFS) from TCGA, we constructed a prognostic senescence-associated lncRNA signature (SenALSig). The OS and DFS were compared between the low- and high- risk groups defined by SenALSig. A single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm were used to investigate the relationship between the predictive signature and immune status. Finally, the relationship between SenALSig and drug treatment options was investigated. An independent CRC cohort and three CRC cell lines were recruited to perform real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis to validate the results discovered in silico.A prognostic risk model consisting of six senescence-associated lncRNAs was constructed, including SNHG16, AL590483.1, ZEB1-AS1, AC107375.1, AC068580.3, and AC147067.1. High-risk scores according to the SenALSig were significantly associated with poor OS (hazard ratio =1.218, 95% confidence interval: 1.140-1.301; P0.001). The model's accuracy was further supported by receiver operating characteristic (ROC) curves (the area under the curve is 0.714) and a principal component analysis (PCA). In univariate and multivariate Cox regression analyses, SenALSig was further found to be a prognostic factor independent of other clinical factors. Furthermore, we discovered that immune checkpoint expression and response to chemotherapy and targeted therapy differed significantly between the SenALSig-stratified high- and low-risk groups. Finally, the qPCR results revealed that the expression levels of the six senescence-associated lncRNAs differed significantly between tumor and normal tissues and between the CRC cell lines and a normal human colon mucosal epithelial cell line.SenALSig can better predict survival and risk in CRC patients, as well as help develop new anti-cancer treatment strategies for CRC.

BackgroundCuproptosis has recently been considered a novel form of programmed cell death. To date, factors crucial to the regulation of this process remain unelucidated. Here, we aimed to identify long-chain non-coding RNAs (lncRNAs) associated with cuproptosis in order to predict the prognosis of patients with hepatocellular carcinoma (HCC).MethodsUsing RNA sequence data from The Cancer Genome Atlas Live Hepatocellular Carcinoma (TCGA-LIHC), a co-expression network of cuproptosis-related mRNAs and lncRNAs was constructed. For HCC prognosis, we developed a cuproptosis-related lncRNA signature (CupRLSig) using univariate Cox, lasso, and multivariate Cox regression analyses. Kaplan-Meier analysis was used to compare overall survival among high- and low-risk groups stratified by median CupRLSig score. Furthermore, comparisons of functional annotation, immune infiltration, somatic mutation, TMB (tumor mutation burden), and pharmacologic options were made between high- and low-risk groups.ResultsOur prognostic risk model was constructed using the cuproptosis-related PICSAR, FOXD2-AS1, and AP001065.1 lncRNAs. The CupRLSig high-risk group was associated with poor overall survival (hazard ratio = 1.162, 95% CI = 1.063– 1.270; p < 0.001). Model accuracy was further supported by receiver operating characteristic and principal component analysis as well as internal validation cohorts. A prognostic nomogram developed considering CupRLSig data and a number of clinical characteristics were found to exhibit adequate performance in survival risk stratification. Mutation analysis revealed that high-risk combinations with high TMB carried worse prognoses. Finally, differences in immune checkpoint expression and responses to chemotherapy as well as in targeted therapy among CupRLSig stratified high- and low-risk groups were explored.ConclusionsThe lncRNA signature constructed in this study is valuable in prognostic estimation in the setting of HCC.

Background The risk of lymph-node metastasis (LNM) in T1 colorectal cancer (CRC) has not been well documented in heterogeneous Western populations. This study investigated the predictors of LNM and the long-term outcomes of patients by analysing T1 CRC surgical specimens and patients’ demographic data. Methods Patients with surgically resected T1 CRC between 2004 and 2014 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with multiple primary cancers, with neoadjuvant therapy, or without a confirmed histopathological diagnosis were excluded. Multivariate logistic-regression analysis was used to identify the predictors of LNM. Results Of the 22,319 patients, 10.6% had a positive lymph-node status based on the final pathology (nodal category: N1 9.6%, N2 1.0%). Younger age, female sex, Asian or African-American ethnicity, poor differentiation, and tumor site outside the rectum were significantly associated with LNM. Subgroup analyses for patients stratified by tumor site suggested that the rate of positive lymph-node status was the lowest in the rectum (hazard ratio: 0.74; 95% confidence interval: 0.63–0.86). Conclusion The risk of LNM was potentially lower in Caucasian patients than in API or African-American patients with surgically resected T1 CRC. Regarding the T1 CRC site, the rectum was associated with a lower risk of LNM.

Background The Chromobox (CBX) protein family, which is a crucial part of the epigenetic regulatory complex, plays an important role in the occurrence and development of cancer; however, the function and prognostic value of CBX family members in gastric cancer is not clear. Methods we investigated the relationship between CBX members and gastric cancer using a range of tools and databases: Oncomine, Kaplan-Meier plotter, cBioPortal, ULCAN, Metascape, and GEPIA. Results The results showed that, relative to normal gastric tissue, mRNA expression levels of CBX1-6 were significantly higher in gastric cancer tissue, whereas the level of CBX7 was significantly lower. Furthermore, overexpression of CBX3-6 and underexpression of CBX7 mRNAs was significantly related to the poor prognosis and survival of gastric cancer patients, making these CBX family members useful biomarkers. Finally, overexpression of CBX1 mRNA was significantly related to the poor prognosis of gastric cancer patients treated with adjuvant 5-fluorouracil-based chemotherapy. Conclusions The members of the CBX family can be used as prognosis and survival biomarkers for gastric cancer and CBX1 may be a biomarker for choosing the chemotherapy regimen of gastric cancer patients.

Background The potential prognostic value of alternative splicing (AS) variants and regulatory splicing factors in gastric carcinogenesis is unclear. We aimed to exploit the aberrant AS signatures and splicing factors involved in gastric cancer (GC) and to determine their prognostic predictive values. Methods We performed detailed data acquisition using the Cancer Genome Atlas project and profiled genome-wide AS signatures in a cohort of 190 patients with stomach adenocarcinoma (STAD). Prognostic prediction models and splicing correlation networks were assessed using an integrative bioinformatics analysis approach. Results We detected 1,308 overall survival (OS)-related AS signatures in 993 genes, most of which were favorable prognostic factors. Six splicing factors have been suggested to be dysregulated in GC, i.e., DHX15, PPP4R2, PRPF38B, RBM9, RBM15, and ILF3. Another notable finding was that most favorable prognosis AS events were positively correlated with expression of splicing factors, while a majority of poor survival prognostic AS genes were negatively associated with the expression of splicing factors. Conclusions To our knowledge, the current study provided the first comprehensive profiling of global modifications in the RNA splicing to identify survival associated AS signatures of GC specific genes. Our findings contribute to a better understanding of aberrant AS signatures and splicing factors in STAD, which can potentially be used as prognostic biomarkers and therapeutic targets for GC.

Background: Zinc finger protein of cerebellum 2 (ZIC2) is a transcriptional activator or repressor that is important for the organogenesis of the central nervous system. Previous studies have reported that ZIC2 is widely upregulated in a variety of tumors. Methods: Oncomine database was used to evaluate the expression levels of ZIC2 in hepatocellular carcinoma (HCC) and normal liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to validate the results from the database. Cox regression analysis and survival curves were performed to assess the survival effect of ZIC2 in HCC. Results: Increased expression of ZIC2 was detected in HCC tissues compared with normal liver tissues. In addition, patients with high ZIC2 levels had a poor prognosis. Multivariate analysis showed that clinical stage (T or M classification) and ZIC2 levels were independent prognostic factors for overall survival. Moreover, a subgroup analysis revealed that patients with moderate or poor grade tumors, T1–2 tumors, N0 tumors, early American Joint Committee on Cancer (AJCC) stage, and old age were more likely to present with overexpression of ZIC2. To conclude, ZIC2 is upregulated in HCC and associated with the histology and survival of HCC patients. Conclusions: The expression status of ZIC2 may serve as an independent prognostic marker of HCC. Keywords: Zinc finger protein of cerebellum 2 (ZIC2), Prognosis, Hepatocellular carcinoma (HCC), Liver, Biomarker

We aimed to explore the potential prognostic impact of the metastatic site on the management approach and prognosis of stage IV colorectal cancer patients with synchronous metastases. Synchronous metastatic colorectal cancer patients reported to the Surveillance, Epidemiology, and End Results Program database between 2010 and 2013 were included in this study. Overall survival (OS) was compared between patients with different treatment options using risk-adjusted Cox proportional hazard regression models. Overall, 17,776 patients with stage IV colorectal cancer were identified. Of these patients, 2,052 (11.5%) underwent surgical resection for tumors at both the primary and meta-static sites. Patients who underwent surgical resection of both primary and metastatic sites with liver, lung, and simultaneous liver and lung metastases had a longer median OS ( P < 0.001) than patients who underwent nonsurgical treatments. Cox regression analysis revealed that surgical resection of both primary and metastatic sites was associated with a significantly enhanced OS ( P < 0.001). Colorectal cancer patients with hepatic or pulmonary metastases, who underwent metastasectomy, even in selected patients with both hepatic and pulmonary metastases after multidisciplinary evaluation, could have a better survival benefit than patients who underwent nonsurgical treatments.

The epigenetic regulators of cellular senescence, especially long non-coding RNAs (lncRNAs), remain unclear. The expression levels of lncRNA were previously known to be prognostic indicators for tumors. We hypothesized that lncRNAs regulating cellular senescence could also predict prognosis in patients with hepatocellular carcinoma (HCC) and developed a novel lncRNA predictive signature.Using RNA sequencing data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) database, a co-expression network of senescence-related messenger RNAs (mRNAs) and lncRNAs was constructed. Using univariate Cox regression analysis and a stepwise multiple Cox regression analysis, we constructed a prognostic HCC senescence-related lncRNA signature (HCCSenLncSig). Kaplan-Meier analysis was used to compare the overall survival (OS) of high- and low-risk groups stratified by the HCCSenLncSig. Furthermore, the HCCSenLncSig risk score and other clinical characteristics were included to develop an HCC prognostic nomogram. The accuracy of the model was evaluated by the time dependent receiver operating characteristic (ROC) and calibration curves, respectively.We obtained a prognostic risk model consisting of 8 senescence-related lncRNAs: AL117336.3, AC103760.1, FOXD2-AS1, AC009283.1, AC026401.3, AC021491.4, AC124067.4, and RHPN1-AS1. The HCCSenLncSig high-risk group was associated with poor OS [hazard ratio (HR) =1.125, 95% confidence interval (CI): 1.082-1.169; P0.001]. The accuracy of the model was further supported by ROC curves (the area under the curve is 0.783, sensitivity of 0.600, and specificity of 0.896 at the cut-off value of 1.447). The HCCSenLncSig was found to be an independent prognostic factor from other clinical factors in both univariate and multivariate Cox regression analyses. The prognostic nomogram shows HCCSenLncSig has a good prognostic effect for survival risk stratification. Finally, we found that a higher number of immunosuppressed Treg cells infiltrate in high-risk patients (P0.001 compared to low-risk patients), possibly explaining why these patients have a poor prognosis. On the other hand, the expression of immunotherapy markers, such as CD276, PDCD1, and CTLA4, was also up-regulated in the high-risk patients, indicating potential immunotherapy response in these patients.The development of HCCSenLncSig allows us to better predict HCC patients' survival outcomes and disease risk, as well as contribute to the development of novel HCC anti-cancer therapeutic strategies.

SummaryBackgroundPeople living with chronic disease, particularly seniors older than 60 years old, are lagging behind in the national vaccination campaign in China due to uncertainty of safety and effectiveness. However, this special population made up of most severe symptom and death cases among infected patients and should be prioritized in vaccination program. In this retrospective study, we assessed the safety and immunogenicity of the CoronaVac inactivated vaccines in people with underlying medical conditions to address the vaccine hesitation in this special population.MethodsIn this cohort study, volunteers aged 40 years and older, had received two doses of CoronaVac inactivated vaccines (3-5 weeks interval), been healthy or with at least one of the six diseases: coronary heart disease (CAD), hypertension, diabetes mellitus (DM), chronic respiratory disease (CRD), obesity and cancer, were recruited from 4 study sites in China. The primary safety outcome was the incidence of adverse events within 14 days after each dose of vaccination. The primary immunogenic outcome was geometric mean titer (GMT) of neutralizing antibodies to living SARS-CoV-2 virus at 14-28 days, 3 months, and 6 months after full two-dose vaccination. This study is registered with ChiCTR.org.cn (ChiCTR2200058281) and is active but no longer recruiting.FindingsAmong 1,302 volunteers screened between Jul 5 and Dec 30, 2021, 969 were eligible and enrolled in our cohort, including 740 living with underlying medical conditions and 229 as healthy control. All of them formed the safety cohort. The overall incidence of adverse reactions was 150 (20.27%) of 740 in the comorbidities group versus 32 (13.97%) of 229 in the healthy group, with significant difference (P=0.0334). The difference was mainly contributed by fatigue and injection-site pain in some groups. Most adverse reactions were mild (Grade 1). We did not observe any serious adverse events related to vaccination. By day 14-28 post vaccination, the seroconversion rates and GMT of neutralizing antibody showed no significant difference between disease group and healthy group, except CAD group (P=0.03) and CRD group (P=0.04) showed slight reduction. By day 90, the neutralizing antibody GMTs were significantly reduced in each group, with no significant difference between diseases and healthy group. By day 180, the neutralizing antibody continued to decrease in each group, but with slower declination.InterpretationFor people living with chronic disease especially seniors older than 60 years, the CoronaVac vaccines are as safe as in healthy people. Although the immunogenicity is slightly different in subgroup of some diseases compared with that of the healthy population, the overall trend was consistent. Our findings highlight the evidence to address vaccine hesitancy for seniors and people living with chronic diseases.FundingYunnan Provincial Science and Technology Department (202102AA100051 and 202003AC100010, China), Sinovac Biotech Ltd (PRO-nCOV-4004).

Background:Leber’s congenital amaurosis (LCA) is a severe hereditary retinopathy disease that is characterized by early and severe reduction of vision,nystagmus,sluggish or absent pupillary responses. To date, the pathogenesis of LCA remains unclear,and the majority cases are caused by autosomal recessive inheritance. In this study, we explored the mutation in the Crumbs homologue 1(CRB1) gene in a Chinese family with LCA. Methods:We conducted comprehensive ocular examinations and collected 5 ml of blood samples from members of a Chinese family with LCA. The pathogenic gene was identified by capturing and sequencing the related genes of ocular diseases.Results: We found a nonsense mutation(c.1499C>G) in the 6th exon of CRB1 in a Chinese family with LCA,which predicted a change of the protein p.S500X,may lead to loss of gene function.Conclusions: This study reported a novel mutation(c.1499C>G,p.S500X) of the CRB1 gene occurred in a Chinese family with LCA, thus expanding the spectrum of CRB1 mutations causing LCA. And we summarize the 76 mutations reported so far in CRB1 that caused LCA8.

Laparoscopic transabdominal preperitoneal hernia repair (TAPP) is one of the most widely used methods in inguinal hernia surgery. After the mesh is placed, the peritoneum must be resutured to avoid contact with the tissues and organs in the abdominal cavity. If the peritoneal suture time is too long, the operation and anesthesia time will be prolonged, increasing the burden on the patient. Moreover, improper suture methods cause serious consequences, such as intestinal obstruction and mesh infection. The straight-needle suture method transforms the three-dimensional spatial configuration of the needle holder and the arc needle tip into a two-dimensional planar structure, which greatly reduces the difficulty of suturing. The three-tailed knot can be anchored at the beginning of the suture by its friction and button effect, which has an exact fixation effect. Thus, the suture does not easily slip, and the time to complete the suturing is shortened. Compared with the traditional suture method, the operator can suture the peritoneum more quickly, beginners can pass through the difficult learning curve faster, and skilled operators can also shorten the total operation time of TAPP to a certain extent. Thus, this suture method is extremely amenable to clinical application.

Aim: Few studies focused on functions and regulatory networks of MUC family members in colorectal cancer based on comprehensive analysis of online database. Materials & methods: Copy number variation, methylation, pathway analysis and drug influence on MUC expression were analyzed based on The Cancer Genome Atlas and GTEx database. Results: Copy number variation analysis showed MUC heterozygous amplification and heterozygous deletion predominate. Methylation of MUC17, MUC12 and MUC4 were found related to gene expression. Function of MUC family genes mainly affects pathways such as apoptosis, cell cycle, DNA damage and EMT pathways. PLX4720, dabrafenib, gefitinib, afatinib and austocystin D can alter the expression of MUC gene. Conclusion: The genetic and epigenetic changes of MUC are related to the level of MUC expression in colorectal cancer.

Background: The epidemiology and clinical outcome of gastroenteropancreatic signet ring cell carcinoma (SRC) were not well illustrated. We aimed to explore the long-term epidemiology and predictors affect the overall survival (OS) of patients with SRC in gastrointestinal tract and pancreas. Methods: Annual age-adjusted incidence, OS and survival trend of patients with gastroenteropancreatic SRC were evaluated in the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2014. Multivariate Cox hazards regression model were used to identify predictive factors of the entity disease. Results: Of the 24,613 patients in the cohort, 54.0% (13,295) were male gender. The age-adjusted incidence of SRC from January 2000 to December 2014 was decreased slightly. This trend appeared across all stages, grades and all the tumor locations, excerpt for esophagus and appendix. In regard to the incidence of SRC in gastrointestinal tract and pancreas, the stomach carried a higher incidence than other sites. Different primary site, stage and grade, and age of clinical diagnosis as well as time period of diagnosis were all found to have the significant median OS by multivariable analysis. Five years’ OS of gastroenteropancreatic SRC was improving gradually between 2000–2014. In subgroups stratified by tumor stages and grades, the most pronounced improvement of survival over the same interval was observed in the early-stage and well differentiation SRC. Conclusions: SRC in a heterogeneous US population tended to carry the poor prognosis with a high proportion of distant metastasis. The poor prognosis of SRC was mainly caused by high tumor stages and poor differentiation at diagnosis.

Acute-on-chronic liver failure (ACLF) is associated with very high mortality. Accurate prediction of prognosis is critical in navigating optimal treatment decisions to improve patient survival. This study was aimed to develop a new nomogram integrating two-dimensional shear wave elastography (2D-SWE) values with other independent prognostic factors to improve the precision of predicting ACLF patient outcomes.A total of 449 consecutive patients with ACLF were recruited and randomly allocated to a training cohort (A ACLF prognostic nomogram was developed with independent prognostic factors, including 2D-SWE, age, total bilirubin (TB), neutrophils (Neu), and the international normalized ratio (INR). The area under the ROC curve (AUC) was 0.849 for the new model in the training cohort and 0.861 in the prospective validation cohort, which were significantly greater than those for MELD (0.758), MELD-Na (0.750), and Jin's model (0.777, allWe established and validated a 2D-SWE-based noninvasive nomogram to predict the prognosis of ACLF patients that was more accurate than other prognostic models.

Background: The combination of preoperative progressive pneumoperitoneum (PPP) and botulinum toxin type A (BTA) in adjuvant treatment of large parastomal hernia (LPH) has not been reported in the previous literature.Methods: From February 2018 to June 2019, 16 patients were diagnosed with LPH in our hospital were included in this study. All patients received PPP and BTA treatment to expand abdominal volume and extend abdominal muscle before surgery. The laparoscopic Sugarbaker method was preferred for defect close.Results: Before and after PPP and BTA, the mean volume of the parastomal hernia (VPH) was 1,522 and 1,644 cc, respectively (P < 0.01), and the mean volume of the abdominal cavity (VAC) was 5,847 and 9,408 cc, respectively (P < 0.01). The VPH/VAC ratio was decreased by an average of 8.4% after the combination management. And the lateral abdominal muscle length was increased by an average of 4.8 cm/side (P < 0.01). These patients underwent surgery successfully, and no hernia recurrence after (17.6 ± 2.4) months of follow-up.Conclusions: The combination of PPP and BTA effectively expand the abdominal volume, decrease the risk of abdominal compartment syndrome (ACS) postoperatively, and beneficial to laparoscopic repair of LPH.

BACKGROUND Investigating molecular biomarkers that accurately predict prognosis is of considerable clinical significance. Accumulating evidence suggests that long non-coding ribonucleic acids (lncRNAs) are frequently aberrantly expressed in colorectal cancer (CRC). AIM To elucidate the prognostic function of multiple lncRNAs serving as biomarkers in CRC. METHODS We performed lncRNA expression profiling using the lncRNA mining approach in large CRC cohorts from The Cancer Genome Atlas (TCGA) database. Receiver operating characteristic analysis was performed to identify the optimal cutoff point at which patients could be classified into the high-risk or low-risk groups. Based on the Cox coefficient of the individual lncRNAs, we identified a nine-lncRNA signature that was associated with the survival of CRC patients in the training set (n = 175). The prognostic value of this nine-lncRNA signature was validated in the testing set (n = 174) and TCGA set (n = 349). The prognostic models, consisting of these nine CRC-specific lncRNAs, performed well for risk stratification in the testing set and TCGA set. Time-dependent receiver operating characteristic analysis indicated that this predictive model had good performance. RESULTS Multivariate Cox regression and stratification analysis demonstrated that this nine-lncRNA signature was independent of other clinical features in predicting overall survival. Functional enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology terms further indicated that these nine prognostic lncRNAs were closely associated with carcinogenesis-associated pathways and biological functions in CRC. CONCLUSION A nine-lncRNA expression signature was identified and validated that could improve the prognosis prediction of CRC, thereby providing potential prognostic biomarkers and efficient therapeutic targets for patients with CRC.

This study aimed to compare the efficacy of laparoscopic and conventional left hemicolectomy for treating colon cancer and their effects on stress response and quality of life of patients.92 patients with colon cancer were selected. Forty three patients in the study group were treated with laparoscopic left hemicolectomy, and 49 patients in the control group were treated with conventional left hemicolectomy. The surgery, postoperative recovery, intraoperative and postoperative complications were compared between the two groups. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL1β and IL-6. The quality of life of patients after surgery was analyzed by the Functional Assessment of Cancer Therapy-Lung (FACT-L).The operation time and intraoperative blood loss of the study group were statistically lower than those of the control group (p0.05). The postoperative exhaust time and hospitalization time of the study group were statistically shorter than those of the control group (p0.05). Serum IL-1β and IL-6 levels in the study group were significantly lower than those in the control group (p0.05). In the two groups, the overall scores of quality of life after surgery were significantly lower than those before surgery (p0.05). After surgery, the overall score of quality of life in the study group was significantly higher than that in the control group (p0.05).The laparoscopic left hemicolectomy with surgical approaches on the surgical plane has high safety and marked efficacy.

There is growing evidence that epithelial mesenchymal-transition (EMT) plays significant roles in terms of tumor metastasis. There are a lot of cytokines inducing EMT of tumor cells, EGF is one of the important cytokines.Ezrin is a connexin between the cytoskeleton and the cell membrane, which is closely related to the morphological movement and metastasis of tumor cells.EGF can activate Ezrin and affects cell motility. In recent years, many studies have shown that NF-kB acts as an important transcription factor, involving in the process of EMT. However, does Ezrin participate in the regulation of EGF-induced EMT through the NF-kB pathway? This question needs us to discuss.In the present study, we found that EGF could induce colorectal cancer cells to develop EMT,enhance their ability to invade and migrate and promotes phosphorylation of Ezrin Tyr353.On the other hand, inhibition of Ezrin could reverse EGF-induced EMT and inhibit NF-kB P65 translocating into the nucleus. Finally, knockout of Ezrin inhibited EGF-induced lung metastasis of colorectal cancer xenografts and abnormal activation of Ezrin and NF-kB were related with colorectal cancer metastasis and poor prognosis. Our present results suggest that Ezrin/NF-kB pathway may provide experimental evidence for new targeted drugs for colorectal cancer metastasis.

SRY-box transcription factors (SOXs) are effective inducers for the formation of stem-like phenotypes. As a member of SOX family, SOX9 (SRY-box transcription factor 9) has been reported to be highly expressed and exert oncogenic functions in multiple human cancers. In this study, we hypothesized that SOX9 could regulate the function of cancer stem/initiating cells (CSCs) to further facilitate the progression of colorectal cancer (CRC). Then, stable transfection of shRNAs was used to silence indicated genes. Loss-of-function experiments were conducted to demonstrate the in vitro function of CRC cells. In vivo study was conducted to determine the changes in tumorigenesis and metastasis in vivo. Bioinformatics analyses and mechanistic experiments were employed to explore the downstream molecules. Presently, GEPIA data indicated that SOX9 was upregulated in 275 COAD (colon adenocarcinoma) samples relative to 349 normal tissues. Besides, we also proved the upregulation of SOX9 in CRC cell lines (HCT15, SW480, SW1116, and HT-29) compared to normal NCM-460 cells. Silencing of SOX9 suppressed cell growth, stemness, migration, and invasion. Mechanistically, SOX9 activated the transcription of lncRNA phenylalanyl-tRNA synthetase subunit alpha antisense RNA 1 (FARSA-AS1), while FARSA-AS1 elevated SOX9 in turn by absorbing miR-18b-5p and augmented FARSA via sequestering miR-28-5p. Furthermore, loss of FARSA-AS1 hindered malignant phenotypes in vitro and blocked tumor growth and metastasis in vivo. Notably, we testified that FARSA-AS1 aggravated the malignancy in CRC by enhancing SOX9 and FARSA. Our study unveiled a mechanism of SOX9-FARSA-AS1-SOX9/FARSA loop in CRC, which provides some clews of promising targets for CRC.

PURPOSE Preoperative progressive pneumoperitoneum (PPP) has not been reported in the management of parastomal hernias; therefore, the present study evaluated its effectiveness in the surgical management of large parastomal hernias. PATIENTS AND METHODS This prospective, observational study included 23 consecutive patients with large parastomal hernias who underwent PPP between January 2016 and September 2018. The volume of parastomal hernia (VPH), volume of the abdominal cavity (VAC), and the VPH/VAC ratio were measured before and after PPP using abdominal computed tomography scan data. All the hernias were repaired by a laparoscopic or laparoscopic-open-laparoscopic approach using the intraperitoneal Sugarbaker technique. RESULTS Before and after PPP, the mean VPH was 1442 and 1581 mL (P

Background: Reports on preoperative progressive pneumoperitoneum (PPP) and botulinum toxin A (BTA) for managing giant inguinoscrotal hernias are limited. Hence, we report our experience with these ...

Objective Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play important regulatory roles in the tumorigenesis and progression of gastric cancer (GC). The aim of this study was to construct the prognostic predictive model of lncRNAs signature and improve the survival prediction of GC. Patients and methods The expression profiling of lncRNAs in large GC cohorts was performed from The Cancer Genome Atlas (TCGA) databases using the lncRNAs-mining approach, including training data set (N = 160) and testing data set (N = 159). A 13-lncRNAs signature significantly associated with overall survival (OS) in the training data set was selected. The prognostic value of this 13-lncRNAs signature was then confirmed in the test validation set and the entire validation set, respectively. Results Based on lncRNA expression profiling of 319 patients with stomach adenocarcinoma (STAD), prognostic 13-lncRNAs signature was found to be significantly associated with the prognosis of GC. Compared to patients with low-risk scores, patients with high-risk scores had a significantly shorter survival time. Moreover, functional enrichment analysis indicated that this 13-lncRNAs signature was potentially involved in multiple biological processes, such as DNA replication and cell cycle signaling pathway. Conclusions The prognostic model of the 13-lncRNAs signature established by our study could improve the survival prediction of GC to a greater extent.

Dysregulation of microRNA (miRNA) is actively involved in the development and progression of gastric cancer (GC). MiR‐520c was previously found to be overexpressed in GC specimens and cells. However, the clinical significance of miR‐520c and its biological function in GC remain largely unknown. Here, we found that miR‐520c expression in GC tissues was significantly increased compared to normal adjacent gastric tissues. Its increased level was prominently correlated with poor clinical parameters and prognosis of GC patients. Accordingly, the expression of miR‐520c was obviously elevated in GC cell lines as compared with gastric epithelial cells. Overexpression of miR‐520c in N‐87 cells significantly increased the proliferative ability, migration, and invasion of cancer cells, while miR‐520c silencing suppressed MKN‐45 cell proliferation, migration, and invasion in vitro. Mechanically, miR‐520c inversely regulated interferon regulatory factor 2 (IRF2) abundance in GC cells. Herein, IRF2 was found to be a downstream target of miR‐520c in GC. Furthermore, IRF2 was down‐regulated in GC tissues compared to nontumor tissues. An inverse correlation between IRF2 and miR‐520c expression was observed in GC cases. Taken together, miR‐520c may serve as a prognostic predictor and a therapeutic target for GC patients.

The aim of this systematic review is to evaluate and compare the efficacy and safety of temporary tube stoma and conventional loop stoma for the protection of a low anastomosis in colorectal cancer. A systematic literature search was performed using PubMed, EMBASE, Science Citation Index, and Cochrane Central Register of Controlled Trails. Primary outcome measures were anastomotic leakage rate, the reoperation rate for anastomotic leakage, and stoma-related complications. Secondary outcome measures were operation time, length of hospital stay, time to stoma closure, and permanent stoma rate. Four studies were carried out and 642 patients (332 with temporary tube stoma and 310 with conventional loop stoma) met the inclusion criteria. The incidences of anastomotic leakage and reoperation rate were statistically similar in tube stoma and loop stoma groups. In comparison with conventional loop stoma, temporary tube stoma was associated with a significantly less stoma-related complications (odds ratio = 0.20; 95% confidence interval [CI]: 0.08–0.50), and shorter operation and hospital stay time (weighted mean difference = -47.28 minutes, 95% CI: -74.68 to -19.88; and weighted mean difference = -5.22 days, 95% CI: -10.32 to -0.13, respectively). Time to stoma closure was significantly shorter in the temporary tube stoma groups (weighted mean difference = -114.58 days, 95% CI: -148.38 to -80.77). Patients receiving temporary tube stoma had lower rates of stoma-related complications, shorter operation and hospital stay time, and stoma closure time. Tube can be easily removed without second surgery in most cases. Therefore, temporary tube stoma is a feasible and effective alternative to conventional loop stoma for the protection of a low colorectal anastomosis.

In recent decades, the incidence and diagnosis of thyroid cancer have risen dramatically, and thyroid cancer has now become the most common endocrine cancer in the world. The onset of thyroid cancer is insidious, and its progression is slow and difficult to detect. Therefore, early prevention and treatment have important strategic significance. Moreover, an in-depth exploration of the pathogenesis of thyroid cancer is key to early prevention and treatment. Substantial evidence supports obesity as an independent risk factor for thyroid cancer. Adipose tissue dysfunction in the obese state is accompanied by dysregulation of a variety of adipocytokines. Adiponectin (APN) is one of the most pivotal adipocytokines, and its connection with obesity and obesity-related disease has gradually become a hot topic in research. Recently, the association between APN and thyroid cancer has received increasing attention. The purpose of this review is to systematically review previous studies, give prominence to APN, focus on the relationship between APN, obesity and thyroid cancer, and uncover the underlying pathogenic mechanisms.

Background Neural stem cells (NSCs) are undifferentiated precursor cells that have the ability to self-renew and proliferate and have the capacity to become either glia (oligodendrocytes and astrocytes) or neurons. NSCs can act as beneficial adjuncts for many neurological disorders, such as cerebral infarction, spinal cord injuries, Alzheimer's disease, and Parkinson's disease. Long noncoding RNAs (lncRNAs) play essential roles during cell differentiation, proliferation, and metabolism. This study aimed to explore the role played by adipocyte differentiation-associated long noncoding RNA (ADNCR) in the self-renewal and multipotency of NSCs. Methods In this study, we identified NSCs and verified that these cells were able to regenerate and differentiate into both astrocytes and neurons. Then we studied the relation between expression of ADNCR and transcription factor 3 (TCF3) and proliferation of NSCs. Results ADNCR and TCF3 expression have been shown to decrease during the differentiation of NSCs into both neurons and astrocyte induction cells. However, the expression of the microRNA miR-204-5p increased over time during the differentiation of NSCs into both neurons and astrocyte induction cells. ADNCR acts as a competing endogenous RNA (ceRNA) for miR-204-5p, and the overexpression of ADNCR suppressed miR-204-5p expression and enhanced TCF3 expression in NSCs, which resulted in enhanced proliferation and suppressed neural differentiation. Conclusions These data suggested that the use of ADNCR may represent a new strategy for expanding the interventions used to treat neurological disorders.

e16665 Background: Hepatocellular carcinoma (HCC) remains a major challenge for public health worldwide and long-term outcomes remained dismal despite availability of curative treatment. We aimed to construct a multi-gene model for prognosis prediction to inform clinical management of HCC. Methods: RNA-seq data of paired tumor and normal tissue samples of HCC patients from the TCGA and GEO database were used to identify differentially expressed genes (DEGs). DEGs shared by both cohorts along with patients’ survival data of the TCGA cohort were further analyzed using univariate Cox regression and LASSO Cox regression to build a prognostic 10-gene signature, followed by validation of the signature via ICGC cohort and identification of independent prognostic predictors. A nomogram for prognosis prediction was built and Gene Set Enrichment Analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Results: Of 571 patients (70.93% men and 29.07% women; median age [IQR], 65 [56-72] years), a signature of 10 genes was constructed using the training cohort. In the testing and validation cohorts, the signature significantly stratified patients into low- vs high-risk groups in terms of overall survival across and within subpopulations with stage I/II and III/IV disease and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 0.13 [95% CI, 0.07-0.24; P < 0 .001] to 0.38 [95% CI, 0.2-0.71; P < 0.001]) after adjusting for clinicopathological factors. Prognosis was significantly worse in the high-risk group than in the low-risk group across cohorts (P < 0.001 for all). The 10-gene signature achieved a higher accuracy (C-index, 0.84; AUCs for 1-, 3- and 5-year OS, 0.84, 0.81 and 0.85, respectively) than 8 previously reported multigene signatures (C-index range, 0.67 to 0.73; AUCs range, 0.68 to 0.79, 0.68 to 0.80 and 0.67 to 0.78, respectively) for estimation of survival in comparable cohorts. A nomogram incorporating tumor stage and signature-based risk group showed better predictive performance for 1- and 3- year survival than for 5 year survival. Moreover, GSEA revealed that the pathways related to cell cycle regulation were more prominently enriched in the high-risk group while the low-risk group had higher enrichment of metabolic process. Conclusions: Taken together, we established a robust 10-gene signature and a nomogram to predict overall survival of HCC patients, which may help recognize high-risk patients potentially benefiting from more aggressive treatment.

Long non-coding (lnc)RNA mortal obligate RNA transcript (MORT) is inhibited in numerous types of cancer in humans, indicating its role as a tumor suppressor. The present study demonstrated downregulation of lncRNA MORT in the tumor tissues of patients with colon cancer. The expression of MORT in tumor tissues was linearly associated with its expression levels in plasma. Low MORT expression was associated with low overall survival rate. Moreover, the overexpression of MORT resulted in decreased, whereas treatment with transforming growth factor β1 (TGF-β1) resulted in increased, invasion and migration rates of colon cancer cells. In addition, TGF-β1 treatment attenuated the inhibitory effect of MORT overexpression on the invasion and migration rates of colon cancer cells. The overexpression of MORT inhibited TGF-β1 expression in colon cancer cells, whereas treatment with TGF-β1 failed to affect the expression of the lncRNA. Therefore, it is postulated that MORT inhibits invasion and migration colon cancer cells by inactivating TGF-β1.

Colorectal cancer (CRC) is a malignancy with high metastatic rates. The mechanism of miR-128 on the regulation of Ribophorin-II (RPN2) in CRC cells was explored in the present study. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blot analyses were conducted to detect miR-128 and RPN2 levels in tissues and cell lines. AmiR-128 overexpression model was constructed using miR-128 mimic transfection in HT29 CRC cells. Then, cell proliferation was detected using a Cell Counting Kit-8 assay, and the migratory and invasive abilities were measured by Transwell assay. RT-qPCR and western blot analysis were used to detect expression levels of protein kinase-B (Akt)-tumor protein 53 (p53)-cyclin pathway and metastasis-associated factors. In the present study, it was identified that aberrant decreased miR-128 was negatively correlated with RPN2 in CRC tissues. The increased RPN2 levels were significantly associated with poorly-differentiated histology, advanced stages and lymph nodes metastasis in patients with CRC. The survival rate of patients with CRC was also closely associated with RPN2 levels. In HT29 cells, miR-128 upregulation downregulated mRNA and protein levels of RPN2, and significantly inhibited cell proliferative, migratory and invasive abilities. Markedly decreased Akt phosphorylation and cyclin D1 levels and increased p53 levels were detected when cells were transfected with miR-128 mimics. Concurrently, decreased levels of matrix metalloproteinase (MMP)-2, MMP-9 and metastasis-associated protein 1, and increased levels of epithelial-cadherin and tissue inhibitor of metalloproteinases 2, were revealed in miR-128 mimic-transfected cells. Subsequent to screening with miRNA target prediction databases, the specificity of miR-128-targeted RPN2 was validated by a luciferase reporter assay. In conclusion, the results suggested that miR-128 was a specific negative regulator of RPN2, which regulated colorectal cancer cell proliferation and migration by affecting the Akt-p53-cyclin pathway. These data may provide novel evidence for the therapeutic potential of miR-128-based treatments for colorectal cancer.

To investigate the efficacy of single-hand four-needle suture with sled-shaped needle three-tail fixed stitch in closure of pesudohernia sac of direct hernia under transabdominal preperitoneal (TAPP) inguinal hernia repair.A randomized controlled trail was conducted on adult patients with unilateral direct inguinal hernia undergoing laparoscopic TAPP repair from January 2014 to January 2018 at the Sixth Affiliated Hospital of Sun Yat-sen University. A total of 156 patients were enrolled prospectively in the study and were randomly divided into single-hand four-needle suture group (trial group, 76 cases) and traditional tacking group (control group, 80 cases). In trial group, sled-shaped needle three-tail knot-free stitch was applied to the continuous four-needle suture. The sled-shaped needle three-tail fixed stitch was made as follows: straighten the tail of a 3-0, 1/2-circle looper VICRYL Rapide into a sled shape; use suture overlap method to make and tighten a single knot; thread the end of the needle into the single knot loop;knot two ends of the thread next to the first knot; tighten the second knot, leaving about 12 cm to the end of the needle;cut the end of the loop (leaving about 0.6 cm) and the other end of the thread(leaving about 1.5 cm). In the control group, a hernia repair tack was used to fix the pseudohernia sac on pectineal ligament. This study was approved by the Hospital Ethics Committee(approval number: L2014ZSLYEC-016). Operation time, pseudoherina sac closure time, hospitalization cost, morbidity of postoperative complication, VAS score and postoperative recurrence were compared between two groups.All the patients completed operations successfully. There were no significant differences between trial group and control group in age [(60.2±0.4) years vs. (61.1±0.7) years)], gender (male ratio 93.4% vs. 92.5%), BMI [(25.1±0.2) kg/mCompared to tack fix method, single-hand four-needle suture with sled-shaped needle three-tail fixed stitch can effectively close pseudohernia sac, reduce hospitalization cost and ameliorate postoperative pain in TAPP repair, which is worth promotion.

Hiatal hernia is a common disease, which is always complicated with gastro-esophageal reflux. However, owing to restriction of diagnosis ability, the finding of hiatal hernia is still at low level in China. How to increase the finding or diagnosis of this disease and improve the life quality of patients, is an important task of radiologists and hernial surgeons. Surgery has been integrated into the therapy of hiatal hernia for a long time, but most surgeons still need to improve their recognition about its essence and the anti-reflux mechanism of lower esophagus. The purpose of surgery of hiatal hernia is not only to repair the defect, but to recover the anatomic structure and function of lower esophagus, as well as to rebuild anti-reflux barrier in stomach at the mean time. The key principle of surgery is to recover structure of GEJ, location of LES and the length of lower esophagus through fundoplication and firm fixation, which prevent it from dislocating to thoracic cavity. By adhering to the principle of this, we can combine the anatomy and function in repair of hiatal hernia, and recover and keep the anti-reflux function of LES utmost. MDT, specialized precision program and standardization will play more and more important roles in hiatal hernia therapy in the future. In this article, we made a review about the diagnosis and therapy history of hiatal hernia, as well as prospected the progress in the near future.

Kruppel-like factor 5 (KLF5) takes part in the pathologic processes of many types of cancer; however, its expression and roles in the biological behavior of gastric cancer remain unknown. TargetScan suggested that miR-145-5p is the predicted effective and conserved microRNA (miRNA) that binds to KLF5 through its 3'-untranslated region (UTR). We investigated the expression of KLF5 and miR-145-5p messenger RNA (mRNA) in gastric cancer and then analyzed its role in the biological behavior of gastric cancer cells. Our results indicated that KLF5 expression was detected by immunohistochemistry in 39.7% of the gastric cancer cases and was increased compared with that of the corresponding noncancerous normal mucosa (0.01 < p < 0.05). The poorly differentiated subtype showed positive KLF5 expression, whereas the differentiated subtype showed negative KLF5 expression (p < 0.05). Dual-luciferase reporter assay suggested KLF5 3'-UTR was the direct target of miR-145-5p. Compared with the differentiated gastric cancer, miR-145-5p was downregulated in undifferentiated gastric cancer (p < 0.05). The downregulation of KLF5 expression and differentiation of MGC-803 and BGC-823 caused by siKLF5 or miR-145-5p mimic transfection. Our results indicated that miR-145-5p/KLF5 3'-UTR affected the differentiation of gastric cancer. miR-145-5p was able to promote gastric cancer differentiation by targeting KLF5 3'-UTR directly. Our data suggest a novel mechanism for cancer differentiation and a new facet to the role of miR-145-5p/KLF5 in gastric cancer.

Xihuang pill (XHP), a traditional Chinese herbal formula, has long been used as an effective agent against multiple tumors. The aim of this study is to evaluate the effects of XHP on the growth inhibition and apoptosis in glioblastoma U-87 MG cells. Gas chromatography-mass spectrometry (GC-MS) was performed for constituent analysis of XHP. Cell viability, cell cycle arrest, generation of reactive oxygen species (ROS), and apoptosis were measured by CCK-8 assay, PI/RNase staining, DCFH-DA assay, TUNEL assay, Annexin V-FITC/PI double staining, and JC-1 assay, respectively. The role of XHP in the regulation of Akt/mTOR/FOXO1 interaction was clarified by using Western Blotting (WB), immunofluorescence (IF), pharmacological inhibitor or antioxidant, and siRNA silencing. The results suggested that XHP could inhibit U-87 MG cells growth and arrest cells in S-phase cell cycle significantly and that the generation of ROS, collapse of mitochondrial membrane potential, enhancement of Bax/Bcl-xL ratio, and reduction of the precursor forms of caspase-9 and caspase-3 caused by XHP prompted that a ROS-mediated mitochondria-dependent apoptosis was possibly involved. Furthermore, XHP affected the Akt/mTOR/FOXO1 pathway via inhibiting the phosphorylation of Akt, mTOR, and FOXO1 and increasing both prototype and nuclear translocation of FOXO1. Inhibition of Akt, mTOR, and FOXO1 by specific inhibitors or siRNA could interpose the apoptotic induction. In conclusion, we demonstrate for the first time that XHP may regulate glioblastoma U-87 MG cell apoptosis via ROS-mediated Akt/mTOR/FOXO1 pathway.

Aberrant expression of musashi2 (MSI‐2) has been detected in several malignancies. However, its role in the progression of colorectal cancer (CRC) remains unknown. Our study was designed to investigate the expression and prognostic significance of MSI‐2 protein in patients with colorectal cancer. The expression of MSI‐2 was detected in 164 patients’ colorectal cancer and control specimens by the tissue microarray technique and immunohistochemical staining. The correlations between MSI‐2 expression and clinicopathological variables including overall survival were analyzed. The prognostic value of liver metastasis is evaluated by logistic regression and receiver operating characteristic (ROC) analysis. MSI‐2 was highly expressed in 32.9% (54/164) of the colorectal cancer. Overexpression of MSI‐2 was associated with depth of invasion, lymph node metastasis, distant metastasis, liver metastasis, Tumor Node Metastasis (TNM) clinical stage, and Carcinoembryonicantigen (CEA) level (P = 0.040, 0.014