Perioperative chemotherapy with docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) for the treatment of locally advanced gastric or gastro-esophageal junction adenocarcinoma (MATCH): an open-label, randomized, phase 2 clinical trial.

BACKGROUND: It remains unclear whether addition of docetaxel to the combination of a platinum and fluoropyrimidine could provide more clinical benefits than doublet chemotherapies in the perioperative treatment for locally advanced gastric/gastro-esophageal junction (LAG/GEJ) cancer in Asia. In this randomized, phase 2 study, we assessed the efficacy and safety of perioperative docetaxel plus oxaliplatin and S-1 (DOS) versus oxaliplatin plus S-1 (SOX) in LAG/GEJ adenocarcinoma patients. METHODS: Patients with cT3-4 Nany M0 G/GEJ adenocarcinoma were randomized (1:1) to receive 4 cycles of preoperative DOS or SOX followed by D2 gastrectomy and another 4 cycles of postoperative chemotherapy. The primary endpoint was major pathological response (MPR). RESULTS: From Aug, 2015 to Dec, 2019,154 patients were enrolled and 147 patients included in final analysis, with a median age of 60 (26-73) years. DOS resulted in significantly higher MPR (25.4 vs. 11.8%, P = 0.04). R0 resection rate, the 3-year PFS and 3-year OS rates were 78.9 vs. 61.8% (P = 0.02), 52.3 vs. 35% (HR 0.667, 95% CI: 0.432-1.029, Log rank P = 0.07) and 57.5 vs. 49.2% (HR 0.685, 95% CI: 0.429-1.095, Log rank P = 0.11) in the DOS and SOX groups, respectively. Patients who acquired MPR experienced significantly better survival. DOS had similar tolerance to SOX. CONCLUSIONS: Perioperative DOS improved MPR significantly and tended to produce longer PFS compared to SOX in LAG/GEJ cancer in Asia, and might be considered as a preferred option for perioperative chemotherapy and worth further investigation.

Risk factors for the occurrence and recurrence of acute cerebellar ataxia: a retrospective observational study.

OBJECTIVE: There is little evidence to support a correlation between abdominal surgery and acute cerebellar ataxia (ACA). We reviewed the records of children with ACA treated at our institution to analyze risk factors for ACA. METHODS: Clinical data of 442 children with ACA treated at Children's Hospital of Nanjing Medical University between November 2015 and June 2019 were retrospectively analyzed. Univariate and multivariate analyses were performed to determine risk factors for the occurrence and recurrence of ACA. RESULTS: In total, 442 children with ACA were included in this study. Multivariate logistic regression analysis showed age (p = 0.009), infection (p < 0.001), vaccination (p < 0.001), head trauma (p < 0.001), intussusception surgery (IS) (p < 0.001), operation for indirect inguinal hernia (p < 0.001), and operation for congenital gastrointestinal malformation (p < 0.001) were independent risk factors for ACA occurrence. Univariate analysis showed that only IS (p < 0.001) was associated with ACA recurrence. CONCLUSIONS: Surgeons should be aware that age, infection, vaccination, head trauma, and history of abdominal surgery are associated with ACA, while IS is a risk factor for ACA recurrence.

Intrauterine exposure to oxidative stress induces caspase-1-dependent enteric nerve cell pyroptosis.

PURPOSE: This study determined whether oxidative stress causes the developmental abnormalities of the enteric nervous system during the embryonic period. METHODS: Using the test results of tissue specimens of children with Hirschsprung disease (HSCR), we established a pregnant rat model of oxidative stress and a cellular oxidative stress model to conduct related molecular, cellular, and histopathological experiments for exploration and validation. RESULTS: The results of the quantitative real-time polymerase chain reaction assay indicated overexpression of pyroptosis markers (NLRP3, ASC, and caspase-1) in HSCR lesions and newborn pups in the oxidative stress group (treated with D-galactose). The expression of cathepsin D was significantly decreased in intestinal tissues of newborn pups in the oxidative stress group compared to the control group. Reactive oxygen species scavengers (N-acetyl-cysteine, NAC), the caspase-1 inhibitor (VX-765), and the NLRP3 siRNA could reverse the release of LDH, decrease the number of propidium iodide stained cells, and reduce the percentage of TUNEL/caspase-3 double-positive cells in the H2O2-treated group. CONCLUSION: Oxidative stress can induce the death of enteric nerve cells by activating caspase-1-dependent pyroptosis through NLRP3 inflammasomes, which may contribute to abnormal enteric nervous system development.

An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer.

BACKGROUND: Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies. METHODS: We examined Crohn's-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load. RESULTS: Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (Ptrend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42-0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12-0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (Pinteraction > 0.2). CONCLUSIONS: The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.

Circular RNA CCDC66 targets DCX to regulate cell proliferation and migration by sponging miR-488-3p in Hirschsprung's disease.

It has been suggested that circular RNAs play critical roles in natural growth and disease development. Nevertheless, whether the circular RNAs were related in Hirschsprung's disease (HSCR) remains unknown. Thus, we discovered the cir-CCDC66 was downregulated in HSCR compared with the normal gut tissues. The cir-CCDC66 reduction might inhibit cells' proliferation and migration in vitro. Then, we found that DCX transcript was putative cir-CCDC66 competing endogenous RNA. Furthermore, the function of cir-CCDC66 as a sponge for miR-488-3p to regulate DCX RNA expression was demonstrated by immunoprecipitation and luciferase reporter assays. In conclusion, this is the first report revealing that cir-CCDC66 modulates DCX expression through sponging miR-488-3p and thus participates in the onset of HSCR.

The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome.

Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74-2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16-3.02) for Bifidobacterium-high cases (Ptrend = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.

Lipopolysaccharide enhances ADAR2 which drives Hirschsprung's disease by impairing miR-142-3p biogenesis.

Researches over the past decade suggest that lipopolysaccharide is a dominant driver of gastrointestinal motility and could damage the enteric neuron of rat or porcine. However, it remains poorly defined whether LPS participates in Hirschsprung's disease (HSCR). Here, we discovered that LPS increased in HSCR tissues. Furthermore, LPS treatment suppressed the proliferation and differentiation of neural precursor cells (NPCs) or proliferation and migration of human 293T cells. ADAR2 (adenosine deaminase acting on RNA2)-mediated post-transcriptional adenosine-to-inosine RNA editing promotes cancer progression. We show that increased LPS activates ADAR2 and subsequently regulates the A-to-I RNA editing which suppresses the miR-142 expression. RNA sequencing combined with qRT-PCR suggested that ADAR2 restrain cell migration and proliferation via pri-miR-142 editing and STAU1 up-regulation. In conclusion, the findings illustrate that LPS participates in HSCR through the LPS-ADAR2-miR-142-STAU1 axis.

Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum.

BACKGROUND & AIMS: Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and tumor necrosis factor-receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on an empiric dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with the presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. METHODS: We calculated EDIP scores based on answers to food frequency questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a polymerase chain reaction assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. RESULTS: During 28 years of follow-up evaluation of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores were associated with increased risk of F nucleatum-positive colorectal tumors (Ptrend = .03); for subjects in the highest vs lowest EDIP score tertiles, the hazard ratio for F nucleatum-positive colorectal tumors was 1.63 (95% CI, 1.03-2.58). EDIP scores did not associate with F nucleatum-negative tumors (Ptrend = .44). High EDIP scores associated with proximal F nucleatum-positive colorectal tumors but not with proximal F nucleatum-negative colorectal tumors (Pheterogeneity = .003). CONCLUSIONS: Diets that may promote intestinal inflammation, based on EDIP score, are associated with increased risk of F nucleatum-positive colorectal carcinomas, but not carcinomas that do not contain these bacteria. These findings indicate that diet-induced intestinal inflammation alters the gut microbiome to contribute to colorectal carcinogenesis; nutritional interventions might be used in precision medicine and cancer prevention.

Erratum: LncRNA AFAP1-AS Functions as a Competing Endogenous RNA to Regulate RAP1B Expression by sponging miR-181a in the HSCR: Erratum.

[This corrects the article DOI: 10.7150/ijms.18392.].

Negative feedback circuitry between MIR143HG and RBM24 in Hirschsprung disease.

Hirschsprung disease (HSCR) is a genetic disorder of neural crest development. It is also believed that epigenetic changes plays a role in the progression of this disease. Here we show that the MIR143 host gene (MIR143HG), the precursor of miR-143 and miR-145, decreased cell proliferation and migration and forms a negative feedback loop with RBM24 in HSCR. As RBM24 mRNA is a target of miR-143, upregulation of RBM24 upon an increase in the level of MIR143HG could be attributed to sequestration of miR-143 by MIR143HG (sponge effect). The RBM24 protein was shown to bind to MIR143HG, and subsequently, accelerated its degradation by destabilizing its transcript and facilitating its interaction with Ago2, thus forming a negative feedback between MIR143HG and RBM24. In addition, experiments using siRNA against DROSHA indicated that RBM24 could promote the biogenesis of miR-143. This feedback loop we describe here represents a novel mode of autoregulation, with implications in HSCR pathogenesis.

Mutations of MYH14 are associated to anorectal malformations with recto-perineal fistulas in a small subset of Chinese population.

BACKGROUND: Anorectal malformations (ARMs) are among the most commonly congenital abnormalities of distal hindgut development, ranging from anal stenosis to anal atresia with or without fistulas and persistent cloaca. The etiology remains elusive for most ARM cases and the majority of genetic studies on ARMs were based on a candidate gene approach. MATERIALS AND METHODS: In all eight family members of a non-consanguineous Chinese family, we performed whole-exome sequencing. Subsequently, exome sequencing of MYH14 in 72 unrelated probands with ARMs was performed. The accurate distribution of non-muscle myosin II heavy chain (NMHC II) was investigated by immunohistochemistry in serial sagittal sections of E11.5-13.5 mouse cloacal regions. RESULTS: A homozygous mutation in MYH14 was identified in the two siblings of family 1. Compound heterozygous MYH14 changes were identified in an unrelated individual. Immunohistochemical analysis suggest stronger NMHC IIC localization in the epithelium of the murine embryonic cloaca, urorectal septum and hindgut compared with another two NMHC II isoforms. CONCLUSION: This is the first identification of mutations in MYH14 as a cause of ARMs. The stronger localization of NMHC IIC in E11.5-13.5 mouse cloacal regions further supports the role of MYH14 in anorectal development.

LncRNA AFAP1-AS Functions as a Competing Endogenous RNA to Regulate RAP1B Expression by sponging miR-181a in the HSCR.

Background: Long noncoding RNAs (lncRNAs) have recently emerged as important regulators in a broad spectrum of cellular processes including development and disease. Despite the known engagement of the AFAP1-AS in several human diseases, its biological function in Hirschsprung disease (HSCR) remains elusive. Methods: We used qRT-PCR to detect the relative expression of AFAP1-AS in 64 HSCR bowel tissues and matched normal intestinal tissues. The effects of AFAP1-AS on cell proliferation, migration, cell cycle, apoptosis and cytoskeletal organization were evaluated using CCK-8, transwell assay, flow cytometer analysis and immunofluorescence, in 293T and SH-SY5Y cell lines, respectively. Moreover, the competing endogenous RNA (ceRNA) activity of AFAP1-AS on miR-181a was investigated via luciferase reporter assay and immunoblot analysis. Results: Aberrant inhibition of AFAP1-AS was observed in HSCR tissues. Knockdown of AFAP1-AS in 293T and SH-SY5Y cells suppressed cell proliferation, migration, and induced the loss of cell stress filament integrity, possibly due to AFAP1-AS sequestering miR-181a in HSCR cells. Furthermore, AFAP1-AS could down-regulate RAP1B via its competing endogenous RNA (ceRNA) activity on miR-181a. Conclusions: These findings suggest that aberrant expression of lncRNA AFAP1-AS, a ceRNA of miR-181a, may involve in the onset and progression of HSCR by augmenting the miR-181a target gene, RAP1B.

Role of MiR-215 in Hirschsprung's Disease Pathogenesis by Targeting SIGLEC-8.

BACKGROUND/AIMS: Hirschsprung's disease (HSCR), known as aganglionosis, is an infrequent congenital gut motility disorder characterized by absence of enteric neurons. In this study, we focus on the role of the intronic miR-215 and its host gene isoleucyl-tRNA synthetase 2 (IARS2) in the pathogenesis of HSCR. METHODS: Quantitative real time PCR and Western blot were used to detect the miRNA, mRNAs, and proteins levels. The dual-luciferase reporter gene assay confirmed the direct regulation of the specific mRNA and miRNAs in cell lines. Transwell assays, CCK8 assay, and flow cytometry were used to measure cell function of the human 293T and SH-SY5Y cells. RESULTS: Expression levels of miR-215 in HSCR patient colon tissues were outstandingly lower than controls, which was positively correlated with expression of the host gene IARS2 and negatively correlated with predicted target gene: sialic acid binding Ig-like lectin 8 (SIGLEC-8). The loss of miR-215 inhibited cell migration and proliferation, which was consistent with the reduction of IARS2. The dual-luciferase reporter gene assay confirmed that miR-215 resulted in the inhibition of SIGLEC-8 by directly binding to the 3'-UTR of SIGLEC-8. Moreover, knocking-down SIGLEC-8 rescued the extent of suppressed cell migration and proliferation that resulted from the diminishment of miR-215. CONCLUSIONS: Our findings indicate that miR-215 acts in concert with the host gene IARS2 to affect neuron migration and proliferation through the target gene SIGLEC-8. We infer that the IARS2-miR-215-SIGLEC-8 pathway may play a crucial role in the pathogenesis of HSCR.

Downregulated Expression of Long Non-Coding RNA LOC101926975 Impairs both Cell Proliferation and Cell Cycle and Its Clinical Implication in Hirschsprung Disease Patients.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to participate in various diseases. Hirschsprung disease (HSCR) is a common digestive disease in the new born. However, the relationship between lncRNAs and HSCR remains unclarified. METHODS: We used qRT-PCR to detect the relative expression of LOC101926975 in 80 pairs of HSCR bowel tissues and matched normal bowel tissues. CCK-8 assay, transwell assay and flow cytometry were then used to evaluate the function in vitro by knocking down the LOC101926975 in SK-N-BE(2) cells. Receiver operating characteristic (ROC) curve was used to evaluate the potential diagnostic value of LOC101926975. RESULTS: LOC101926975 was significantly downregulated in HSCR tissues with excellent correlation with FGF1. Dysregulation of LOC101926975 suppressed cell proliferation and induced G0/G1 arrest without impact on cell apoptosis or migration. Meanwhile, the AUC of LOC101926975 was 0.900 which presented great diagnostic value. CONCLUSIONS: Our study firstly investigates the potential function of LOC101926975 in HSCR and infers that LOC101926975 can distinguish HSCR from the normal ones.

[Characteristics of recurrence in patients with gastric cancer after radical gastrectomy and adjuvant chemotherapy].

OBJECTIVE: To analyze the characteristics of recurrence in gastric cancer patients after radical gastrectomy and adjuvant chemotherapy. METHODS: The clinicopathological data of 110 gastric cancer patients who developed recurrence or second primary malignancies after radical gastrectomy and adjuvant chemotherapy with FOLFOX4 regimen or docetaxel plus FOLFOX4 regimen were analyzed retrospectively. RESULTS: The median time to recurrence was 13.9 months (range, 1.7 to 63.1 months), and the median overall survival was 27.4 months (range, 6.9 to 90.7 months) in the whole group. The median survival time after recurrence was 10.1 months (range, 0.3 to 73.9 months). 82 (74.5%) patients had recurrence within 2 years after gastrectomy. The modes of surgical procedure and lymph node dissection influenced significantly on the time to recurrence (P<0.05 for both). Among the 110 patients with recurrence, 46 (41.8%) patients had peritoneal metastases, 33 (30.0%) had hematogenous metastases and 32 (29.1%) had locoregional lymph node metastases. Single, double, triple and quatro recurrences were observed at the first time of relapse in 78 (70.9%), 21(19.1%), 9(8.2%) and 2 cases (1.8%), respectively. Patients who developed simultaneous quatro recurrence had the poorest prognosis with a median overall survival of 15.2 months, significantly shorter than that of patients with single recurrence (31.8 months, P=0.003). Patients with peritoneal recurrence died most quickly ( mean 5.6 months), and patients with surgical field recurrence alone survived longest (mean 17.1 months). CONCLUSIONS: Peritoneal, hematogenous and locoregional lymph node metastases are the most frequent recurrences after radical gastrectomy and adjuvant chemotherapy in patients with gastric cancer. Single recurrence occurred in most patients at the first relapse. Combination with other adjuvant treatments should be considered besides adjuvant chemotherapy in gastric cancer patients after radical gastrectomy.

[Risk factors for Clostridium difficile-associated diarrhea among cancer patients].

OBJECTIVE: The aim of this study was to investigate the prevalence of Clostridium difficile (C. difficile) infection and the risk factors for acquisition of C. difficile-associated diarrhea (CDAD) among cancer patients who received chemotherapy or radiation therapy. METHODS: We analyzed 277 stool samples from cancer patients with diarrhea between Sep 2010 and Dec 2011 in our hospital. Stool C. difficile toxin A/B test, stool culture for C. difficile and routine stool examination were performed. In addition, the risk factors for CDAD were investigated in a set of 41 C. difficile toxin-positive cancer patients and 82 matched C. difficile toxin-negative controls by univariate analysis and multivariate analysis. RESULTS: Out of a total of 277 cancer patients with diarrhea, 41 (14.8%) were C. difficile toxin-positive. Among these 41 cases, 11 (26.8%, 11/41) were C. difficile culture-positive. Univariate analysis showed that antibiotics use (P = 0.853), proton pump inhibitor use (P = 0.718), hypoproteinemia (P = 0.139) and white blood cell count (P = 0.454) did not appear to be associated with acquisition of CDAD in cancer patients. However, receiving chemotherapy (P = 0.023), receiving radiotherapy (P = 0.003), a positive fecal occult blood test result (P = 0.005) and the presence of fecal leukocytes (P = 0.007) showed close association with acquisition of CDAD in cancer patients. Multivariate analysis showed that receiving chemotherapy (OR, 8.308; 95% CI, 1.997-34.572; P = 0.004) and a positive result of fecal occult blood test (OR, 8.475; 95% CI, 1.463-49.109; P = 0.017) were independent risk factors for acquisition of CDAD among cancer patients. CONCLUSIONS: Our results support that receiving chemotherapy and a positive fecal occult blood test result are independent risk factors for acquisition of CDAD among cancer patients. Cancer patients who are at high-risk for CDAD should take stool C. difficile toxin A/B test and stool culture for C. difficile regularly and prevention of CDAD.

Leptomeningeal metastasis from solid tumors: a single center experience in Chinese patients.

Leptomeningeal metastasis (LM) is a devastating complication of solid tumors. A retrospective study was carried out to evaluate the outcome and prognostic factors of LM. Patients with LM were identified through MRI from January 2008 to August 2011. 46 patients were included. 32 had NSCLC, five had breast cancer and nine had other cancers. Treatment included radiotherapy in 49 %, intrathecal chemotherapy in 12 %, and systemic chemotherapy in 61 % of the patients. The median survival was 4.4 (range, 0-45) months. KPS score, radiotherapy and systemic treatment were significantly associated with survival. Eighteen (58 %) of NSCLC patients received EGFR-TKI therapy, with a median survival of 13 months. EGFR-TKI therapy was identified as an independent prognostic factor for survival in the NSCLC subgroup. The prognosis remains poor in patients with LM from solid tumors. KPS ≥ 70, systemic treatment and radiotherapy represent positive prognostic factors. EGFR-TKI therapy improves outcomes of LM in selected NSCLC patients.

[Analysis of the prognosis of 111 patients with gastric cancer or adenocarcinoma of the esophagogastric junction combined with pleural or abdominal effusion].

OBJECTIVE: To explore the prognostic factors in patients with gastric cancer (GC) or adenocarcinoma of the esophagogastric junction (AEG) combined with malignant pleural and/or abdominal effusion. METHODS: Clinicopathological data of 111 GC or AEG patients with malignant pleural and/or abdominal effusion treated in our hospital from January 2001 to December 2010 were retrospectively analyzed. RESULTS: The median survival time for the whole group of 111 patients was 6 months. Effusion disappeared in 12 patients, was reduced in 36 cases, with no changes in 15 cases, and increased in 48 patients. The effusion control rate was 56.8%. Effusion was better controlled in female patients, with simple abdominal ascites, Karnovsky performance scores ≥ 80, with no liver metastases, effusion at initial diagnosis, and effective response to systemic chemotherapy.Univariate analysis showed that patients of female sex, Karnovsky performance scores ≥ 80, effusion present at initial diagnosis, simple abdominal ascites, minimal volume of effusion, absence of liver metastasis, control of effusion, initial treatment with effusions and effective response to systemic chemotherapy, normal hemoglobin, albumin, direct and indirect bilirubin levels showed better prognosis (all P < 0.05). Multivariate analysis showed that liver metastases, control of effusions were independent prognostic factors in patients with gastric cancer and adenocarcinoma of the esophagogastric junction (all P < 0.05). CONCLUSIONS: Female patients, simple abdominal ascites, KPS scores ≥ 80, ascites at initial diagnosis, no liver metastases and effective systemic chemotherapy seem to have a better control of the malignant effusion. Patients with no liver metastases and effective control of effusion have a longer survival time.

Mechanism of Endogenous Peptide PDYBX1 and Precursor Protein YBX1 in Hirschsprung's Disease.

Endogenous peptides, bioactive agents with a small molecular weight and outstanding absorbability, regulate various cellular processes and diseases. However, their role in the occurrence of Hirschsprung's disease (HSCR) remains unclear. Here, we found that the expression of an endogenous peptide derived from YBX1 (termed PDYBX1 in this study) was upregulated in the aganglionic colonic tissue of HSCR patients, whereas its precursor protein YBX1 was downregulated. As shown by Transwell and cytoskeleton staining assays, silencing YBX1 inhibited the migration of enteric neural cells, and this effect was partially reversed after treatment with PDYBX1. Moreover, immunoprecipitation and immunofluorescence revealed that ERK2 bound to YBX1 and PDYBX1. Downregulation of YBX1 blocked the ERK1/2 pathway, but upregulation of PDYBX1 counteracted this effect by binding to ERK2, thereby promoting cell migration and proliferation. Taken together, the endogenous peptide PDYBX1 may partially alleviate the inhibition of the ERK1/2 pathway caused by the downregulation of its precursor protein YBX1 to antagonize the impairment of enteric neural cells. PDYBX1 may be exploited to design a novel potential therapeutic agent for HSCR.