Objective : To elucidate the effect of phosphorylation modification at the threonine 592 (Thr592) site on the inhibition of gastric cancer proliferation by sterile alpha motifs and HD structural domain－containing protein 1 (SAMHD1) and the potential mechanism of action． Methods: Post-translational modifications (PTMs) of SAMHD1 protein in gastric cancer tissues and cell lines in the database were analyzed，and immunohistochemical stai- ning was performed to detect SAMHD1 Thr592 phosphorylation in paired tissues of gastric cancer patients．In gastric cancer cells，SAMHD1 Thr592 variants were constructed and transiently transfected，and cell proliferation was detected using the cell counting kit 8 ( CCK-8 ) method． The phosphorylation of the cyclin-dependent kinases ( CDK) 2 protein threonine 160 (Thr160) site was inhibited by the addition of different concentrations of the CDK6 inhibitor，Palbociclib，which reduced the level of SAMHD1 protein Thr592 phosphorylation．Three online databases were used to analyze the SAMHD1 reciprocal proteins and take the intersection to derive the Nik-related kinase (NRK) protein．Immunoprecipitation ( Co-IP) ，mass spectrometry and Western blot were used to verify the interactions between SAMHD1 and NRK proteins and detect the effect of NRK on the phosphorylation of the SAMHD1 Thr592 site. Results : Compared with PTMs such as ubiquitination，the highest level of phosphorylation modification of SAMHD1 was observed in tumors，and the difference was statistically significant (P＜0. 01) ．Immunohistochemical experiments showed that phosphorylated SAMHD1 (Thr592) was expressed higher in gastric adenocarcinoma than that in normal mucosal tissue adjacent to the cancer，and the difference was statistically significant (P < 0. 01) ．Western blot assay showed that SAMHD1 protein expression was elevated in MKN-45 cells in the overexpression wild type and mutant groups ，and phosphorylated SAMHD1 levels were also elevated in the wild type， T592E and HD / AA groups． CCK-8 assay showed that both SAMHD1 wild type and T592A could inhibit gastric cancer cell proliferation，while T592E and HD / AA had no effect on gastric cancer proliferation． On the basis of overexpression of SAMHD1，CCK-8 suggested that cell proliferation was inhibited after adding different concentrations of Palbociclib treatment，and Western blot assay suggested that the phosphorylation level was also reduced. NRK protein was obtained by Co-IP and mass spectrometry identification to screen the SAMHD1 reciprocal protein profile and database intersection，and NRK was found to interact with SAMHD1 protein and promote phosphorylation at SAMHD1 Thr592 site by Co-IP and Western blot assay． Conclusion Phosphorylation of the Thr592 site contributes to the loss of SAMHD1 's ability to inhibit gastric cancer cell proliferation，which is reversed by Palbociclib．NRK interacts with SAMHD1 protein，promoting phosphorylation of the SAMHD1 Thr592 site.

OBJECTIVETo explore the risk factors of vascular invasion in patients with early gastric cancer (EGC), and to investigate the influence of vascular invasion on the prognosis of EGC patients.

METHODSFrom January 2014 to December 2015, 449 EGC patients underwent curative gastrectomy at the First Affiliated Hospital of Anhui Medical University, of whom 27 cases (6.0%) developed vascular invasion. Clinicopathological and follow-up data of EGC cases were analyzed retrospectively. The association between clinicopathological features and vascular invasion was analyzed by using the Chi-square test or Fisher exact test, and the independent risk factors influencing vascular invasion were identified with logistic regression. The influence of vascular invasion on overall survival was investigated with Kaplan-Meier curve. This study was approved by Ethics Committee of The First Affiliated Hospital of Anhui Medical University (No. 2018-03-12).

RESULTSOf 449 EGC patients, 325 were males and 124 were females (ratio 2.6:1.0) with the mean age of (60.8±10.5) (27 to 87) years; 228 were diagnosed as T1a stage and 221 were diagnosed as T1b. Univariate analysis showed that incidence of vascular invasion in EGC patients with ulceration or scar was 8.4%(18/225), which was higher than 3.8%(9/234) in those without ulceration, and the difference was statistically significant (χ²=4.061, P=0.044). The incidence of vascular invasion in patients with low differentiated tumor was 8.8% (20/226), which was significantly higher than 3.1%(7/223) in those with middle-high differentiated tumor(χ²= 8.363, P=0.012). The incidence of vascular invasion in patients staging T1b was 10.9% (24/221), which was significantly higher than 1.3% (3/228) in those staging T1a (P=0.000); The incidence of vascular invasion in patients with lymph node metastasis was 27.3% (15/55), which was significantly higher than 3.0%(12/394) in those without lymph node metastasis (χ²=50.122, P=0.000). However, there were no significant associations of vascular invasion with gender, age, surgical type, multiple tumor, tumor deposit, tumor location and tumor size (all P > 0.05). Multivariate analysis showed that T1b stage (RR=4.653, 95%CI:1.293-16.747, P=0.019) and lymph node metastasis(RR=7.302, 95%CI: 3.063-17.408, P=0.000) were independent risk factors for vascular invasion in EGC patients. Among 449 EGC patients, 444 received complete follow-up(98.9%), including 26 cases with vascular invasion and 418 cases without vascular invasion. The overall survival in vascular invasion group was significantly lower than that in non-vascular invasion group (χ²=60.463, P=0.000). Besides, 198 EGC patients gained follow-up for 3 years, and the 3-year survival rates of 11 vascular invasion cases and 187 non-vascular invasion cases were 54.5% and 96.8% respectively.

CONCLUSIONSThe risk of vascular invasion is higher in EGC patients with lymph node metastasis and tumor infiltrating the submucosa. The prognosis of EGC patients with vascular invasion is poor.

Adult ; Aged ; Aged, 80 and over ; Female ; Gastrectomy ; Humans ; Lymph Node Excision ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; pathology ; surgery ; Vascular Neoplasms

Objective To assess the prognostic significance of prognostic nutritional index (PNI),neutrophil lymphocyte ratio (NLR) and platelet-lymphocyte ratio in gastric cancer patients.Methods Clinico-pathological data of 257 patients with gastric cancer in the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2011 was analyzed retrospectively.The ROC curve and Youden index were used to determine the cut-off value,survival curves were described by KaplanMeier method and compared by Log-rank test.The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors.Results PNI was positively correlated with ages,tumor size,depth of tumor invasion,TNM stages,albumin,pre-albumin and hemoglobin (all P ＜ 0.05).NLR was associated with the tumor size,the depth of invasion,lymph node metastasis,TNM stages,albumin,pre-albumin and hemoglobin (all P ＜ 0.05).PLR was associated with the tumor size,prealbumin and hemoglobin (all P ＜ 0.05).The Kaplan-Meier curves showed that gastric cancer patients had longer overall time in the low NLR group,low PLR group and high PNI group than in the high NLR group,high PLR group and low PNI group respectively (all P ＜ 0.05).The multivariate analyses showed that PNI and NLR were independent factors for predicting overall survival of gastric cancer patients.Conclusions PNI and NLR have more predictive value of overall survival than the PLR,PNI and NLR are independent prognostic factors of OS (overall survival) in gastric cancer.

Objective To investigate the prognostic factors and influencing factors of lymph node ratio (LNR) in patients with Siewert Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction (AEG).Methods The retrospective case-control study was conducted.The clinicopathological data of 444 patients with Siewert Ⅱ and Ⅲ AEG who were admitted to the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2011 were collected.All the 444 patients underwent radical D2 lymph node dissection,extent of lymph node dissection was inferior mediastinum,around the esophageal hiatus and celiac lymph node.Follow-up usingtelephone interview and outpatient examination was performed to detect patients' prognosis once every 3 months within 2 years postoperatively,once every 6 months from 2 vears to 5 years postoperatively and once every 12 months after 5 years up to October 2016.Observation indicators:(1) follow-up and survival situations;(2) univariate and multivariate factors analysis affecting prognosis of patients with Siewert Ⅱ and Ⅲ[AEG;(3) univariate and multivariate factors analysis affecting LNR of patients with Siewert Ⅱ and Ⅲ AEG.The survival curve and rate were respectively drawn and calculated by the Kaplan-Meier method.The univariate analysis and multivariate analysis were respectively done using the Log-rank test and the COX regression model.Results (1) Follow-up and survival situations:all the 444 patients were followed up for 1-81 months,with a median time of 52 months.The 1-,3-,5-year overall survival rates of 444 patients were respectively 93.2％,60.3％ and 45.7％.(2) Factors analysis affecting prognosis of patients with Siewert Ⅱ and Ⅲ AEG:results of univariate analysis showed that tumor diameter,tumor differentiation,invasion depth of tumor,pN staging and staging of LNR were related factors affecting prognosis of patients with Siewert Ⅱ and Ⅲ AEG,with statistically significant differences (x2 =12.332,5.898,36.045,38.847,46.464,P＜0.05).Results of multivariate analysis showed that invasion depth of tumor and staging of LNR were independent factors affecting prognosis of patients with Siewert Ⅱ and Ⅲ AEG [RR =1.393,1.411,95％ confidence interval (CI):1.137-1.708,1.106-1.801,P＜0.05].(3) Factors affecting LNR of patients with Siewert Ⅱ and Ⅲ AEG:results of univariate analysis showed that tumor diameter,tumor differentiation and invasion depth of tumor were related factors affecting LNR of patients with Siewert Ⅱ and Ⅲ AEG,with statistically significant differences (x2=20.077,12.618,36.586,P＜0.05).Results of multivariate analysis showed that tumor diameter,tumor differentiation and invasion depth of tumor were independent factors affecting LNR of patients with Siewert Ⅱ and Ⅲ AEG (OR=0.684,0.688,0.788,95％ CI:0.485-0.965,0.505-0.936,0.687-0.903,P＜0.05).Conclusions The invasion depth of tunor and staging of LNR are independent factors affecting prognosis of patients with Siewert Ⅱ and Ⅲ AEG.Tumor diameter,tumor differentiation and invasion depth of tumor are independent factors affecting LNR of patients with Siewert Ⅱ and Ⅲ AEG.

Objective To explore the independent risk factors of lymph-node metastasis (LNM) in patients with early gastric cancer (EGC),and establish a risk-prediction model based on LNM.Method 962 early gastric cancer patients undergoing curative radical gastrectomy in the First Hospital of Anhui Medical University from July 2011 to April 2016 were enrolled in this study.The relationships between different clinicopathologic characteristics and LNM were analyzed by Chi-square test or Fisher exact probability,and the independent risk factors were determined using Logistic regression analysis.Moreover,LNM risk was stratified and a risk-predicting model was established on the basis of the identified independent risk factors for LNM.Further,the risk-predicting model was validated using 962 EGC cases.The discriminatory accuracy of risk-predicting model was measured by area under ROC curve (ROC-AUC).Results Mucosal differentiated cancer ≤2 cm,irrespective of the existence of an ulcer,had low LNM rates (LNMR ＜ 3.0％).Univariate and multivariate analysis revealed that female EGC patients with submucosal,undifferentiated,vessel invasion and tumor size ＞ 2 cm were independent risk factors of LNM for EGC patients,and relative risks were 1.893,3.173,1.956,1.922 and 9.027 respectively (P ＜ 0.05).ROCAUC of risk-predicting model was 0.768 (P ＜ 0.01),which showed high diagnostic accuracy and sensitivity.Conclusion Female EGC patients with submucosal undifferentiated carcinomas measuring ＞ 2 cm with vessel invasion have higher risk of LNM.

Objective To explore the value of preoperative D-dimer in patients with gastric cancer in judging gastric cancer metastasis and assessing prognosis.Methods Clinicopathological data of 132 patients with gastric cancer in the First Affiliated Hospital of Anhui Medical University between Jan.2010 and Jan.2011 was analyzed retrospectively in this study.All patients were divided into two groups according to the cutoff value (1.465 mg/L)of D-dimer and the relationships between D-dimer and clinicopathological data were determined by chi-square test.Moreover,the association of preoperative D-dimer and the prognosis was analyzed by Kaplan-Meier analysis and Log-rank test.Univariate and multivaritate Cox model were used to analyze the factors which might affect the survival of the patients and significant independent factors.Results A total of 132 patients were enrolled in this study in accordance with the inclusion criteria.D-dimer was positively correlated with the depth of invasion (x2 =4.996,P ＜ 0.05),age (x2 =4.311,P ＜ 0.05) and distant metastasis of gastric cancer (x2 =16.641,P ＜0.01),but not with thc gcndcr,lymph node metastasis,tumor size,the degree of differentiation and TNM stage (P ＞ 0.05).The mean D-dimer level was (1.39 ± 0.7) mg/L in distant metastasis patients and (0.97 ±0.83) mg/L in non distant metastasis patients (P =0.023),the mean plasma D-dimer level in patients alive at the 5 years after the surgery was (0.78 ± 0.58) mg/L,which was significantly lower than the amounts determined for the deceased patients (0.75 ± 0.58) mg/L (P ＜ 0.01).The Kaplan-Meier curves showed that the patients with gastric cancer had a longer time in the low D-dimer group than in the high D-dimer group,showing a significant difference between the two groups (P ＜ 0.01).Univariate analysis showed that the overall survival rate was significantly correlated with the gender,D-dimer,tumor size,the depth of invasion,lymph node metastasis and TNM stage (P all ＜ 0.05).The D-dimer was proved to be independent risk factor for the prognosis of gastric cancer by multivariate analysis(P ＜ 0.05).Conclusion According to the analysis,D-dimer may be valuable biomarker for metastasis patients,besides,D-dimer was an independent prognostic factor for patients with gastric cancer.

To date,gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide.The prognosis of GC is not always satisfactory because of late diagnosis.Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained.While traditional serum assays have limited sensitivity and specificity,gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor.Herein,the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed.The detection of gastric juice pH,fluorescence spectrum,cytology,Helicobacterpyloriassociated markers,nitrosamines,conventional tumor markers,amino acids,proteomics,microRNAs,long noncoding RNAs,protein-coding genes,vitamin C,etc.,and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases.Particularly,early GC may be efficiently screened using gastric juice.Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy,such as pancreatic leakage,fistula,and abscess.Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications.The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.

OBJECTIVETo explore the effect of body mass index (BMI) on postoperative short-term prognosis and survival rate of gastric cancer patients.

METHODSClinical and follow-up date of 153 gastric cancer cases undergoing radical operation in our hospital from January to June 2010 were retrospectively analyzed. According to BMI, patients were divided into low group (BMI<18.5, 23 cases), normal group (18.5≤BMI<25.0, 95 cases) and high group (BMI≥25.0, 35 cases). Clinicopathological features and outcomes were compared the among three groups.

RESULTSAmong three groups, the differences in operation time, intraoperative blood loss, number of lymph node retrieved, postoperative hospital stay, lymph node metastasis rate, tumor staging and postoperative complication morbidity were not statistically significant (all P>0.05). Preoperative hemoglobin in the low group was significantly lower as compared to normal and high groups [(106.1±13.8) g/L vs. 113.5±5.2) g/L and (123.5±8.7) g/L, F=3.265, P=0.041], and so was the preoperative albumin [(38.7±2.5) g/L vs. (41.3±0.8) g/L and (43.5±1.4) g/L, F=8.516, P=0.000]. The ratio of gastric cardiac cancer in the low group was significantly lower as compared to the normal and high groups[34.8%(8/23) vs. 68.4%(65/95) and 62.9%(22/35), χ(2)=8.913, P=0.012]. Five-year survival rate of the low, normal and high groups were 43.5%, 50.5% and 65.7% respectively(P=0.189). Subgroup analysis showed that the 5-year survival rate of patients with gastric cardiac cancer in the low group was significantly lower as compared to those in the high group (25.0% vs. 84.6%, P=0.004).

CONCLUSIONSBMI dose not generally play a role in short-term outcomes and long-term survival of the gastric cancer patients. Nutritional improvement and body weight maintenance may be beneficial to low BMI patients, especially those with gastric cardiac cancer.

Blood Loss, Surgical ; Body Mass Index ; Gastrectomy ; Humans ; Length of Stay ; Lymph Nodes ; Lymphatic Metastasis ; Neoplasm Staging ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Survival Rate ; Treatment Outcome

Despite the gradual improvement in surgical treatment techniques and surgical instruments, the complications and mortality of gastric cancer patients after gastrectomy remain high because of an increased proportion of advanced age and incidence of preoperative morbidity in these patients. Therefore, reducing the peri-operative adverse outcomes in gastrectomy is highly significant. According to published literature, the risk factors of morbidity and mortality may include age, TNM stage, ASA score, POSSUM score, complication, surgeon workload, hospital operation volume, lymphadenectomy scope, combined multiple organ resection, and gastrecto-my type. This review summarizes the recent progress in the risk factors for the mortality and morbidity of gastrectomy.

Clinical data of 23 locally recurrent rectal cancer patients underwent radical anterior resection and 69 controls matched by age and gender was retrospectively analyzed to find out the risk factors related to local recur-rence after radical anterior resection of rectal carcinoma. Univariate analysis showed that tumor size, number of positive lymph nodes, distance between tumor and the anal verge and T stage were risk factors for locally recurrent rectal cancer after radical anterior resection. The results of logistic regression analysis showed that T stage ( T4 stage) was an independent risk factor correlated with the tumor recurrence after radical anterior resection and loca-tion of tumor( distance of tumor from the anal verge being less than 5 cm) seemed to be an independent risk factor correlated with the tumor recurrence.