N6-Methyladenosine Modification Patterns and Tumor Microenvironment Immune Characteristics Associated With Clinical Prognosis Analysis in Stomach Adenocarcinoma.

Background: N6-methyladenosine (m6A) modification is a part of epigenetic research that has gained increasing attention in recent years. m6A modification is widely involved in many biological behaviors of intracellular RNA by regulating mRNA, thus affecting disease progression and tumor occurrence. However, the effects of m6A modification on immune cell infiltration of the tumor microenvironment (TME) are uncertain in stomach adenocarcinoma (STAD). Methods: The Cancer Genome Map (TCGA) database was used to download transcriptome data, clinicopathological data, and survival data for m6A-regulated genes in 433 STAD tissues that meet the requirements of this study. GSE84437 data were obtained from the Gene Expression Omnibus (GEO) database. The correlation between 23 m6A regulated genes was analyzed using R software. Sample clustering analysis was carried out on the genes of the m6A regulatory factor, and survival analysis and differentiation comparison were made for patients in clustering grouping. Then, the Gene Set Enrichment Analysis (GSEA), the single-sample GSEA (ssGSEA), and other methods were conducted to assess the correlation among m6A modification patterns, TME cell infiltration characteristics, and immune infiltration markers. The m6A modification pattern of individual tumors was quantitatively evaluated using the m6A score scheme of the principal component analysis (PCA). Results: From the TCGA database, 94/433 (21.71%) samples were somatic cell mutations, and ZC3H13 mutations are the most common. Based on the consensus, matrix k-3 is an optimal clustering stability value to identify three different clusters. Three types of m6A methylation modification patterns were significantly different in immune infiltration. Thus, 1028 differentially expressed genes (DEGs) were identified. The survival analysis of the m6A score found that patients in the high m6A score group had a better prognosis than those in the low m6A score group. Further analysis of the survival curve combining tumor mutation burden (TMB) and m6A scores revealed that patients had a significantly lower prognosis in the low tumor mutant group and the low m6A score group (p = 0.003). The results showed that PD-L1 was significantly higher in the high m6A score group than in the low score group (p < 2.22e-16). The high-frequency microsatellite instability (MSI-H) subtype score was significantly different from the other two groups. Conclusions: This study systematically evaluated the modification patterns of 23 m6A regulatory factors in STAD. The m6A modification pattern may be a critical factor leading to inhibitory changes and heterogeneity in TME. This elucidated the TME infiltration characteristics in patients with STAD through the evaluation of the m6A modification pattern.

Isoperistaltic versus antiperistaltic uncut Roux-en-Y anastomosis after distal gastrectomy for gastric cancer: a propensity score matched analysis.

BACKGROUND: The uncut Roux-en-y anastomosis (URYA) has some clinical advantages after distal gastrectomy (DG). Little evidence exists regarding the influence of peristalsis on this anastomosis. We aimed to evaluate short-term outcomes of isoperistaltic URYA (iso-URYA) comparing with antiperistaltic URYA (anti-URYA) after DG. METHOD: Patients who underwent URYA for gastric cancer (GC) between January 2016 and December 2018 were selected from Shanghai Changhai Hospital, Navy Medical University. Short-term outcomes were compared between iso-URYA group and anti-URYA group after 1:1 propensity score matching (PSM). RESULT: A total of 612 patients were selected. 392 patients underwent iso-URYA and 220 patients underwent anti-URYA. After PSM, 183 patients for each group were included in the final analysis. No differences were found between them in terms of short-term complications, nutritional status and quality of life 1 year after surgery. Endoscopic examination showed that anti-URYA group had more severe gastritis (P = 0.036). In addition, the recanalization rate was significantly higher when the afferent loop was blocked by stapler. CONCLUSION: The iso-URYA and anti-URYA group present similar results in short term outcomes. Ligation blocking afferent loop leads to lower recanalization rate.

The clinicopathologic factors analysis of early mixed signet ring cell in gastric carcinoma / 实用肿瘤学杂志

Objective To analyze the clinic pathologic factors and survival rate by performing a retro-spective study on the early gastric carcinoma (EGC)with signet ring cell underwent curative gastrostomy (SRC) percentage less than 50%after operation .Methods A total of 424 patients was diagnosed as EGC from January 2008 to January 2010 in Changhai Hospital .The patients were divided into three groups according to the different percentage of SRC within tumor cells , SRC group ( with percentage of SCR more than 50%) , Mixed SRC group (with percentage of SRC less than 50%),and Non-SRC group(Classic adenocarcinoma without SRC ).Then we evaluated the clinic pathologic indicators and prognoses , and study on the relationship with histologic types . Results In ECG,the mixed-SRC group was similar to the SRC group on the phases of onset age and sex .On the other phases,the mixed-SRC group was more associated with mucosa -confined,lower lymph node metasta-sis(LNM),and 5-year survival rate was better than adenocarcinoma group (P<0.05).However,the mixed-SRC group showed more submucosal invasion ,and higher LNM than other groups ( P<0 .05 ) .The mixed-SRC component was one of the independent risk factors of LNM .Conclusion In EGC,mixed-SRC had a more favor-able risk factor of LNM ,showed more aggressive behavior than other groups and displayed poor prognosis .

A case report:Alimentary track hemorrhage caused by mesentery Kaposiform hemangioendothelioma and literature review / 实用肿瘤学杂志

Kaposiform hemangioendothelioma ( KHE ) is a vascular tumor characterized by intermediate malignancy.Retrospective analysis and literature review on the clinical pathologic,immunohistochemical and clini-cal data of a patient with mesentery KHE.The cardinal symptom of this patient is alimentary track hemorrhage, imageological diagnosed as a huge soft tissue mass of mesentery and invaded ileum.Clinical feature is without Ka-sabach-Merritt phenomenon,observing under the light microscope.The tumor is with cavernous vascular structure, and lymphocyte infiltration inside of stroma.The nodules are composed of disposed and lots of short spindle cell tumor;the tumor cells inside of the nodules are vertical and horizontal staggered and form tendon like or fissuring vessels.Immunohistochemistry:CD31(+),CD34(+),D2-40(+),C-Kit(-),SMA(-),Ki-67(1%).

Autologous transplantation of endothelial progenitor cells to prevent multiple organ dysfunction syndromes in pig.

BACKGROUND: It was observed that the number and function of endothelial progenitor cells (EPCs) decreased sharply in the progression of multiple organ dysfunction syndrome (MODS), and it may be the main pathogenesis for MODS. We aim to perform autologous transplantation of EPCs on animal models of MODS to investigate whether EPCs might be used to prevent MODS caused by severe sepsis. METHODS: A total of 60 pigs were randomly divided into three groups: subjected to hemorrhagic shock + resuscitation + endotoxemia only (MODS group); performed autologous transplantation of EPCs after hemorrhagic shock + resuscitation + endotoxemia (transplantation group); and control group. Mononuclear cells of animals of the transplantation group were isolated by density-gradient centrifugation for ex vivo expansion, and the six-passage EPCs labeled with 5-carboxyfluorescein diacetate succinimidyl ester were autologously transplanted at a density of 1 × 10(7) cells/kg body weight at the 24th hour after endotoxemia. The function of important organs was monitored continuously to assess the effects of autologous transplantation of EPCs on MODS. RESULTS: All animals of the MODS group developed MODS (100%), and 17 (85%) of 20 animals died because of MODS; the incidence of MODS and mortality rate in the transplantation group were 45% (9 of 20 pigs; p < 0.01) and 35% (7 of 20 pigs; p < 0.01). In transplantation group, the incidence of pulmonary dysfunction, cardiac dysfunction, hepatosis, and renal dysfunction were 40%, 10%, 5%, and 15%, respectively. The capillary densities of important organs, including the heart, liver, kidney, intestine, and lung, after autologous transplantation of EPCs were significantly higher than those in the MODS group (p < 0.01). CONCLUSION: Autologous transplantation of EPCs could migrate to injured organs and induce angiogenesis to restore blood flow that could improve the function of important organs. It could prevent the incidence of MODS and reduce mortality rate caused by trauma and severe sepsis. Autologous transplantation of EPCs would be a novel, cell-based, vascular endothelium-targeted therapeutic strategy for MODS.

The analysis of 21 cases with multiple injuries in the use of damage control operation / 中国医师进修杂志

Objective To analyze the methods and strategy of treatment for multiple injuries in the use of damage control operation, and improve the treatment level and cure rate for multiple injuries.Method From March 2005 to March 2009, 21 patients with multiple injuries were treated by damage control strategy and performed the determinacy operation after the resuscitation in ICU. Results In 21 patients, 16 cases (76.2%) were cured and 5 cases (23.8%) were dead. The injury severity score of 5 dead cases were exceeded 35 points. Conclusions In the strategy of damage control operation, the surgical operation is considered to be a part of the total resuscitative procedure, not the ending of treatment. To those multiple injuries patients, it is safe and effective to perform the damage control operation. It has practical value in clinical treatment.

The expression of Her-2 in patients with pancreatic carcinoma and its significance / 中国医师进修杂志

Objective To explore the expression of Her-2 and the effect on the initiation,development,invasion and metastasis of pancreatic carcinoma.Methods A total of 225 patients with pancreatic carcinomafrom January 2000 to December 2007 were analyzed retrospectively.Paraffin sections of surgical specimens from all the patients who underwent standard resection were examined by SP immunohistochemical method staining.The expression of Her-2 in patients with pancreatic carcinoma and the association between Her-2 and other clinical and pathological parameters were examined.Results Her-2 was positive in 87 of all the 225 patients(38.67%).The differentiation of tumors;size of tumors;lymph node metastasis and other organs metastasis were significantly related to Her-2.The surrival time of the Her-2-positive patients[(19.33±8.15)/nonths]Was significantly shorter than that of the Her-2-negative patients [(36.23±15.44)months]in the univariate analysis(P<0.01).At multivariate COX proportional hagards model analysis,the positivity of Her-2 applied to be an independent prognostic factor,which was also influenced by size of tumors;lymph node metastasis and other organs metastasis.Conclusion It suggests the incidence of Her-2 play an important role in evaluation of the prognosis of pancreatic carcinoma,and it could serve as an independent predictor of prognosis of pancreatic carcinoma.

Endothelial progenitor cells modulated by IL-1β in multiple organ dysfunction syndrome in porcine / 中华急诊医学杂志

Objective To investigate the modulation of EPCs by interleukin 1β (IL-1β) and p38 mitogen activated protein kinase (p38MAPK) and the pathogenesis resulting from their dysdifferenfiation after trauma.Method Thirty pigs were divided into a control group (n = 15) and a multiple organ dysfimction syndrome (MODS) group (n = 15), the latter of which were subjected to a "two-hit" injury including hemon'hagic shock and endotoxemia. Phosphorylation of p38MAPK in peripheral blood mononuclear cells was monitored by western blotting. The concentration of IL-1β in peripheral blood plasma was determined by ELISA and the numbers of EPCs with FCM in peripheral blood plasma were monitored. The morbidity rates in the two groups were compared by chi square test. The levels of phosphorylation of p38MAPK in peripheral blood mononuclear cells, the concentmtions of IL-1β in peripheral blood plasma and the numbers of EPCs in the peripheral blood were compared between groups using with Student's t lest. Results The level of p38MAPK phosphorylation was more augmented and the concen-tration of IL-1β higher in peripheral blood mononuelear cells and plasma from MODS pigs compared with those from control pigs; nevertheless the mauler of EPC conspicuously decreased in the peripheral blood (P <0.01). The morbidity rate in the MODS group was much higher than that in the control group (P < 0.01). There were fewer EPCs in the peripheral blood of animals in group M than in the peripheral blood of animals in group C (P <0.01). Conclusions p38MAPK phosphorylation is important for the pathogenesis of MODS. p38MAPK phospho-rylation might cause the concentration of IL-1β in the peripheral blood plasma to rise and could cause a drop in the numbers of EPCs, thereby aggravating the inflanmmatory reaction in MODS.

The effect of perineural invasion on overall survival in patients with gastric carcinoma.

AIMS: The availability of different treatment options for gastric carcinoma has reopened the question of correct definition of high-risk categories, which may help in identifying patients with high risk for poor prognosis who would benefit more from adjuvant therapy after operation. Perineural invasion (PNI) seems to provide useful information for management. Therefore, we examined the effect of PNI on overall survival (OS) in patients with gastric carcinoma and the association between PNI and other clinical and pathological factors. PATIENTS AND METHODS: A total of 1,632 patients with gastric carcinoma from 2000 to 2005 were analyzed retrospectively. Paraffin sections of surgical specimens from all patients who underwent gastric resection were stained with laminin. If carcinoma cells infiltrated into the perineurium or neural fascicles, PNI was assessed as positive. Survival analysis was done in 1,372 patients with T1-T4 tumors who underwent curative resection. RESULT: PNI was positive in 518 of the 1,632 patients (31.7%). The size of tumors, T stage, differentiation of tumor, and clinical stage were significantly related to PNI positivity. The proportion of large tumors was significantly higher in PNI-positive patients than in PNI-negative patients (P < 0.01). As the depth of gastric mural invasion or clinical stage increased, the positive rate of PNI also increased. The OS of the PNI-positive patients was significantly shorter than that of the PNI-negative patients in the univariate analysis (P < 0.01). At multivariate Cox proportional hazards model of OS analysis, the positivity of PNI appeared to be an independent prognostic factor for OS (hazards ratio [HR] = 3.23, 95%CI = 2.6-8.11, P < 0.01), which was also influenced by tumor differentiation, T stage, and clinical stage (P < 0.01). CONCLUSION: Our results suggested that the incidence of PNI was high in gastric carcinoma and that it corresponded to the progression of disease. It could provide additional information for identifying patients who are at high risk for poor prognosis. PNI can be a candidate for a new kind of prognostic parameters.