LncRNA NEAT-2 regulate the function of endothelial progenitor cells in experimental Sepsis model.

BACKGROUND: Sepsis is a life-threatening disease with a limited effectiveness and the potential mechanism remains unclear. LncRNA NEAT-2 is reported to be involved in the regulation of cardiovascular disease. This study aimed to investigate the function of NEAT-2 in sepsis. METHODS: We built sepsis animal model with Male Balb/C mice induced by cecal ligation and puncture (CLP). A total of 54 mice were randomly assigned into eight groups: sham operation group (n = 18), CLP group (n = 18), CLP plus si-control group (n = 3), CLP plus si-NEAT2 group (n = 3), CLP plus mimic control group (n = 3), CLP plus miR-320 group (n = 3), CLP plus normal saline group (n = 3), and normal control group (n = 3). The number of peripheral endothelial progenitor cells (EPCs), the expression level of NEAT-2 and miR-320 were detected during progression of sepsis, as well as the number of peripheral EPCs and level of TNF-α, IL-6, VEGF, ALT, AST and Cr. In addition, the function of EPCs was evaluated after NEAT-2 knockdown and miR-320 overexpression in vitro. RESULTS: The number of circulating EPCs increased significantly in sepsis. NEAT-2 expression was significantly increased in the progress of sepsis, accompanied with miR-320 downregulated. NEAT-2 knockdown and miR-320 overexpression attenuated hepatorenal function and increased cytokines in sepsis. Moreover, NEAT-2 knockdown and miR-320 overexpression decreased the proliferation, migration and angiogenesis of endothelial progenitor cells in vitro. CONCLUSIONS: LncRNA-NEAT2 regulated the number and function of endothelial progenitor cells via miR-320 in sepsis, which may contribute to the development of novel potential clinical therapy for sepsis.

XIST as a valuable biomarker for prognosis and clinical parameters in diverse tumors: a comprehensive meta- and bioinformatics analysis.

Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been found dysregulated in a variety of human tumors and influenced the clinicopathologic characteristics in cancer patients. Therefore, we systematically searched relevant literature that has identified the correlation of lncRNA XIST expression and clinical outcomes of tumor patients and conducted this meta-analysis to elucidate the clinical prognostic value of long noncoding RNA XIST in human tumors. A comprehensive literature search was performed from PubMed, Web of Science, EMBASE, and Cochrane library databases up to August 1, 2019. Pooled hazard ratios (HRs) or odds ratios (ORs) with a 95% confidence interval (95% Cl) were calculated to evaluate the prognosis, as well as the clinicopathological parameters of XIST, respectively. We also further validated this meta-analysis using The Cancer Genome Atlas (TCGA) dataset. The outcome revealed that XIST overexpression in tumor tissue was interacted to a poor overall survival (OS) (HR=0.52, 95% CI: 0.44-0.61, p<0.0001), disease-free survival (DFS) (HR=0.50; 95% CI: 0.36-0.69, p<0.0001), tumor type (digestive system malignancies, HR=0.53; 95% CI: 0.44-0.63, p<0.0001); nondigestive system malignancies, HR=0.48; 95% CI: 0.34-0.67, p<0.0001), lymph node metastasis(LNM) (OR=0.61, 95% CI: 0.37-1.00; p=0.048), differentiation (OR=1.46; 95% CI: 0.94-2.29; p=0.096), distant metastasis (DM) (OR=0.48, 95% CI: 0.31-0.75; p=0.001), tumor size (OR=0.59, 95% CI: 0.38-0.92; p=0.019), and tumor stage (OR=2.36; 95% CI: 1.62-3.43; p<0.001). XIST could have potential value in early diagnosis and result in prediction and provide a novel view for the therapeutic target in clinical application.

Analysis of risk factors and prevention strategies for functional delayed gastric emptying in 1243 patients with distal gastric cancer.

BACKGROUND: Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. METHODS: Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. RESULT: In multivariable analysis, age (OR 1.081, 95% CI, 1.047-1.117), BMI (OR 1.233, 95% CI, 1.116-1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829-8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325-6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632-7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963-5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086-1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003-1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068-0.785) was independent protective factor of FDGE. CONCLUSION: Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.

Development and validation of a nomogram for preoperative prediction of lymph node metastasis in early gastric cancer.

BACKGROUND: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. METHODS: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. RESULTS: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. CONCLUSIONS: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.

A case report of gastric cancer with brain metastasis: Rare peripheral nervous system symptoms.

Gastric cancer with brain metastasis is rare. The present study reports a case of gastric cancer with isolated brain metastasis 1 year after gastrectomy. To the best of our knowledge, there have been no prior reports of solitary brain metastasis from gastric cancer with peripheral nervous system symptoms. A distal gastrectomy was performed on a 60-year-old male patient with gastric cancer in November 2012. Postoperative pathological analysis revealed a moderately differentiated adenocarcinoma with tumor invasion into the serosa and metastasis to one dissected lymph node. No abnormalities were found at follow-up examination. However, a tumor representing metastasis to the brain was recognized by a cranial enhanced magnetic resonance imaging examination 1 year after gastrectomy, which was performed when the patient exhibited numbness and thigmesthesia. The patient was administered 30 Gy of stereotactic radiotherapy, delivered in 5 fractions. The patient succumbed to disease 10 months subsequent to undergoing radiotherapy. This case report suggests that gastric cancer may re-present as brain metastasis with peripheral nervous system symptoms.

Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy.

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

[Changes in endothelial progenitor cells and their implications in multiple organ dysfunction syndrome caused by trauma in pigs].

OBJECTIVE: To investigate characteristics of changes in bone marrow endothelial progenitor cells (EPCs) and implications on multiple organ dysfunction syndrome (MODS) as a result of trauma. METHODS: Eighteen mini-pigs were randomized into two groups: MODS group (n=9) and control group (n=9). The animal models of MODS were reproduced by "two-hit" injury with hemorrhagic shock and lipopolysaccharide (LPS) injection. Bone marrow and peripheral blood of them were collected at five time points: normal condition (T1), before injection of LPS (T2), and 0 (T3), 24 (T4) and 48 hours (T5) after injection of LPS. Erythrocytic lysate was added to the samples, and the number of leucocytes in every sample was counted. The rate of EPCs in each sample was determined by flow cytometry. Number of EPCs in bone marrow and peripheral blood were calculated, and the results were analyzed statistically. RESULTS: The number of EPCs (x10(6)/L) in bone marrow of control group at T1-5 was 7.64+/-0.68, 7.32+/-0.55, 7.58+/-1.13, 7.77+/-0.70, and 7.88+/-0.84, respectively, and in peripheral blood control group was 3.54+/-0.26, 4.06+/-0.64, 3.74+/-0.55, 3.61+/-0.37, and 3.98+/-0.63, respectively. The number of EPCs (x10(6)/L) in bone marrow in the experimental group was 7.45+/-1.55, 6.58+/-0.80, 11.27+/-1.20, 10.88+/-1.15, and 8.36+/-2.88, respectively. The number of EPCs (x10(6)/L) in peripheral blood in the experimental group was 3.21+/-0.48, 8.71+/-2.04, 5.98+/-0.77, 1.27+/-0.91, and 2.14+/-0.96, respectively. The number of EPCs in bone marrow of experimental group was larger than that of control group at T3, T4, T5. The number of EPCs in the experimental group in peripheral blood was larger than that of control group at T2, T3, T4, T5. The number of EPCs in bone marrow was larger than that in peripheral blood at every time point (all P<0.05). CONCLUSION: The number of EPCs in peripheral blood elevates sharply in the earlier period, then plummeted quickly during MODS after a trauma. While the number of EPCs in bone marrow descends mildly at first, then rises obviously. Along with the aggravation of MODS, a declination of EPCs in bone marrow emerges. The change in bone marrow EPCs plays an important role in recovery of MODS.

[Isolation, culture and identification of rabbit bone marrow-derived vascular endothelial progenitor cells].

The aim of study was to set up a suitable method of isolation, culture and identification of endothelial progenitor cells (EPC) derived from rabbit bone marrow. Density gradient centrifugation was used to isolate mononuclear cells from bone marrow, the isolated mononuclear cells were cultured with specific culture medium for EPCs. EPCs were identified by cellular morphologic observation, immunohistochemistry testing, flow cytometry and the function test of taking up Dil-ac-LDL and FITC-UEA-1. The results indicated that the newly isolated bone marrow-derived mononuclear cells exhibited a round appearance, following culture for 48 hours, adherent cells grew in colony cluster, presenting with round or irregular appearance, and nuclear division was obvious. On day 7, flaky cell colonies mutually connected together, presenting with spindle-shaped cells. Immunohistochemistry testing in the EPCs showed CD133(+), CD34(+), VIII factor(++), KDR(++); flow cytometry testing showed that the positive rate of CD133 was (18.23+/-7.12)%, the positive rate of CD34 was 47.71+/-14.85%, the positive rate of CD31 was (71.61+/-13.51)%, the positive rate of KDR was (87.24+/-11.40)%. And more than 80% EPC could take up both Dil-acLDL and FITC-UEA-1. It is concluded that the mononuclear cells isolated from bone marrow by density gradient centrifugation can differentiate into EPCs under special culture situation.

[Influences of the phosphorylation of p38 mitogen activated protein kinase on gene expression of tumor necrosis factor-alpha in multiple organ dysfunction syndrome in pigs].

OBJECTIVE: To investigate that the phosphorylation of the p38 mitogen activated protein kinase (p38MAPK) influences gene expression of tumor necrosis factor-alpha (TNF-alpha) in multiple organ dysfunction syndrome (MODS) in pigs. METHODS: Thirty pigs were divided into MODS group and control group, and an animal model of MODS of "two-hit" injury, including hemorrhagic shock and endotoxemia, was reproduced. The content of p38MAPK's phosphorylation was assessed with Western blotting. TNF-alpha mRNA in peripheral blood monocytes was assayed with real time-polymerase chain reaction (RT-PCR). TNF-alpha was monitored in the peripheral blood plasma with enzyme linked immunosorbent assay (ELISA). RESULTS: Phosphorylation of p38MAPK was obviously increased in extent, which enhanced gene expression of TNF-alpha and then secretion of TNF-alpha by the peripheral blood mononuclear cell in MODS, and the differences were statistically significant compared with that of control group (P<0.05 or P<0.01). CONCLUSION: p38MAPK's phosphorylation is important in pathogenesis of MODS, and phosphorylation of p38MAPK can enhance TNF-alpha mRNA transcription and secretion of TNF-alpha from peripheral blood mononuclear cells, which is the mechanism of increased TNF-alpha in MODS.

The change and effect of endothelial progenitor cells in pig with multiple organ dysfunction syndromes.

INTRODUCTION: The dysfunction and decrease of endothelial progenitor cells (EPCs) may play a very important role in the initiation of organ dysfunction caused by trauma or severe sepsis. We aim to measure the number and function of EPCs in the progression of multiple organ dysfunction syndromes (MODS) caused by severe sepsis, which may help to understand the pathogenesis of MODS by the changing of EPCs. METHODS: A total of 40 pigs were randomly divided into two groups, which were subjected to hemorrhagic shock, resuscitation and endotoxemia (experimental group, n = 20) or acted as a control (control group, n = 20). The number and function of EPCs including adhesive, migratory and angiogenesis capacities were analyzed at different times in both groups. RESULTS: All the animals in the experimental group developed MODS (100%) and 17 of 20 animals (85%) died due to MODS; the incidence of MODS and death of the animals in the control group were 0% (P < 0.01). The number, migratory and adhesive capacities of EPCs decreased sharply in the animals of the experimental group corresponding to the increasing severities of MODS, but the angiogenesis function increased gradually until death. The decrease in function of EPCs preceded the decrease in number of EPCs. The decrease in number and function of EPCs occurred prior to the occurrence of MODS. CONCLUSIONS: For the first time, it was observed that the number and function of EPCs decreased sharply in the progression of MODS and that it was prior to the occurrence of MODS. The decrease in number and function of EPCs may be one of the main pathogenic factors of MODS.

[Value of dynamic subtraction technique of magnetic resonance imaging in preoperative TNM-staging assessment of gastric carcinoma].

OBJECTIVE: To explore the value of dynamic subtraction technique of magnetic resonance imaging MRI in preoperative TNM-staging assessment of gastric carcinoma. METHODS: MRI was performed in 39 patients with gastric carcinoma diagnosed by postoperative pathology.The results of MRI were prospectively analyzed by one professor and compared with the corresponding pathological findings. RESULTS: In comparison with pathological results, the accuracy of MRI for T stage was 82.1%, for N stage was 71.8%, and for M stage was 84.6% respectively. The accuracy of MRI for TNM stage was 71.8%, which revealed concordance between the preoperative TNM-staging and postoperative pathological findings (Kappa= 0.671-0.763, P<0.05). CONCLUSION: MRI plays an important role in the assessment of invasion depth of gastric carcinoma, lymph node and distant organ metastases,which has unique priority in preoperative TNM-staging assessment of gastric carcinoma.

Clinical management of abdominal trauma.

OBJECTIVE: To improve the prognosis of patients with abdominal trauma. METHODS: Between January 1993 and December 2005, 415 patients were enrolled in this research. The patients consisted of 347 males and 68 females with mean age of 36 years (ranging from 3-82 years). All abdominal traumas consisted of closed traumas (360 cases, 86.7%) and open traumas (55 cases, 13.3%). RESULTS: A total of 407 cases (98.1%) were fully recovered from trauma and the other 8 cases (1.9%) died of multiple injuries. The mean injury severity score (ISS) of all patients was 22 while the mean ISS of the patients who died in hospital was 42. Postoperative complications were seen in 9 patients such as infection of incisional wounds (6 cases), pancreatic fistula (2 cases) and intestinal fistula (1 case). All these postoperative complications were cured by the conservative treatment. CONCLUSION: Careful case history inquisition and physical examination are the basic methods to diagnose abdominal trauma. Focused abdominal ultrasonography is always the initial imaging examination because it is non-invasive and can be performed repeatedly with high accuracy. The doctors should consider the severity of local injuries and the general status of patients during the assessment of abdominal trauma. The principle of treatment is to save lives at first, then to cure the injuries. Unnecessary laparotomy should be avoided to reduce additional surgical trauma.