Background::Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism.Methods::We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments.Results::The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion::The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration::No. NCT00454519 (https://clinicaltrials.gov/)

Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical N-‍(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Humans ; Signal Transduction ; Stomach Neoplasms/drug therapy* ; Reactive Oxygen Species/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2 ; Cell Line, Tumor

Objective:To study the expression of FOXP3 in gastric cancer and its prognostic significance.Methods:One hundred and six specimens of gastric adenocarcinoma confirmed by pathology from the Department of Gastrointestinal Surgery of the Second People′s Hospital of Lianyungang in Jan. 2005 to Dec. 2015 were selected as the observation group and 85 normal para-cancer tissues as the control group. The expression of FOXP3 in 106 cases of gastric cancer was detected by tissue microarray and immunohistochemical technology. Cox regression model was used to analyze the correlation between survival data and prognosis, and Kaplan-Meiers was used to analyze the relationship between FOXP3 expression and the prognosis of gastric cancer patients.Results:The positive rate of FOXP3 expression was 53.8% (57/106) in gastric cancer tissues and 28.2% (24/85) in paraneoplastic tissues, and the difference was statistically significant ( χ2=12.597, P<0.001). The level of FOXP3 expression in gastric cancer tissues was significantly correlated with the TNM stage of patients′ tumors ( χ2=4.402, P<0.05). Single-factor Cox survival analysis showed that age, tumor pathological grade, tumor size, whether it invaded lymph nodes, TNM stage, FOXP3 expression level and prognosis were correlated.Kaplan-Meier survival analysis showed that the survival rate of tumor cell FOXP3-positive group was lower than that of FOXP3-negative group; in the subgroup type, among the subgroups, any age group, any sex group, stage Ⅲ and Ⅳ tumor cell subgroups, low- and undifferentiated groups, tumor size <16 cm 3 group, and tumor cell FOXP3 expression-positive group invading lymph nodes had lower survival than tumor cell FOXP3 expression-negative group. Conclusions:The expression of FOXP3 is up-regulated in gastric cancer. The expression of FOXP3 in gastric cancer may be a prognostic factor, and the positive expression of FOXP3 may indicate a worse prognosis.

Objective:To explore the application value of enhanced recovery after surgery (ERAS) in colorectal cancer patients.Methods:From January 2017 to December 2018, 60 patients with colorectal cancer who admitted to the Second People′s Hospital of Lianyungang were selected and divided into ERAS group and control group according to the random digital table method, with 30 patients in each group.The inflammation, nutritional indicators, immune indicators and clinical manifestations before and after surgery in the two groups were compared.Results:At 1 d and 3 d after surgery, the C-reactive protein (CRP) levels in the ERAS group were (70.2±10.3)mg/L, (82.5±8.2)mg/L, respectively, which were lower than those in the control group [(81.5±9.9)mg/L, (110.2±12.9)mg/L] ( t=4.324, 9.911, all P<0.05). On the third day after operation, the levels of albumin and prealbumin in the ERAS group were (31.6±4.8)g/L, (196.8±40.6)g/L, respectively, which were higher than those in the control group [(28.0±5.8)g/L, (172.1±38.8)g/L]( t=2.621, 2.409, all P<0.05). The immune parameters(IgA, IgM, IgG, CD 4+, CD 4+ /CD 8+) in the ERAS group were higher than those in the control group( t=2.132, 2.223, 6.063, 4.253, 2.828, all P<0.05). The number of cases with thirsty and hunger on the day of surgery in the ERAS group was 3 cases and 7 cases, respectively, which were less than 21 cases and 25 cases of the control group(χ 2=22.500, 21.696, all P<0.05). The first exhaust time, defecation time and hospital stay time in the ERAS group were (36.2±12.1)h, (63.4±13.4)h and (9.5±3.2)d, respectively, which were shorter than those in the control group [(54.7±13.8)h, (96.5±18.8)h and (12.1±4.0)d] ( t=5.513, 7.845, 2.761, all P<0.05). The incidence of complications between the two groups had no statistically significant difference ( P>0.05). Conclusion:ERAS can significantly reduce the physical and psychological traumatic stress of patients with colorectal cancer, achieve rapid recovery, improve the treatment effect, shorten the length of hospital stay, reduce social and family burden, and provide a basis for the choice of clinical treatment program.

Objective: To compare the effects of laparoscope and open complete mesocolic excision (CME) in the treatment of right colon cancer. Methods: The retrospective case-control study was adopted.The clinical data of 139 patients with right colon cancer who underwent CME at the Second People's Hospital of Lianyungang from January 2014 to November 2017 were collected.The patients were divided into laparoscopy group(55 cases) and open group(84 cases). The postoperative recovery and oncology efficacy were compared. Results: The operation time in the laparoscopy group[(172.8±25.9)min]was longer than that in the open group[(142.3±20.6)min](t=7.387, P<0.05), but the blood loss of the laparoscopy group[(111.6±36.7)mL] was less than that in the open group[(150.1±61.1)mL](t=4.017, P<0.05). There was no statistically significant difference in numbers of lymph nodes harvested.Compared with open group, there were advantages in the laparoscopy group such as less anal exhaust time, less postoperative eating liquid diet time and shorter hospitalization time, the differences were statistically significant (t=4.695, 5.517, 4.642, all P<0.05). There was no statistically significant difference in postoperative complication rate (P>0.05). There were no statistically significant differences in the cumulative recurrence rate, cumulative survival rate and cumulative survival rate between the two groups after 3 years (all P>0.05). Conclusion Laparoscopic CME is minimally invasive and quick recovery, and laparoscopic CME has the same oncologic clearance effects, and is worthy of clinical application.

Objective: To explore the application effect of preoperative administration of immunomodulating enteral nutrition for gastric cancer. Methods: From January 2016 to December 2017, 90 cases with gastric cancer in the Second People′s Hospital of Lianyungang were selected and randomly divided into observation group, control group A and control group B, with 30 cases in each group.The observation group was given enteral nutrition emulsion(TPFT, Ruineng) before and after operation, the control group A was given Ruineng before operation and the enteral nutrition emulsion(TP, Ruisu) after operation, the control group B was given Ruisu before operation and Ruineng after operation.The recovery, serum markers of nutritional status and immune function were evaluated and compared, and the postoperative situations were observed. Results: There were no statistically significant differences in the total protein, albumin, prealbumin and transferrin among the three groups during admission, 1 day before operation and 5 days after operation(all P>0.05). There was no statistically significant difference in immune indicators among the three groups during admission and 1 day before operation(all P>0.05). At 5 days after operation, IgA, IgM, IgG, CD₄⁺ and CD4/CD8 in the observation group were (2.9±0.6)g/L, (1.4±0.4)g/L, (12.4±0.9)g/L, (37.4±5.1)%, (2.2±0.7), respectively, which were significantly higher than those in the control group A[(2.3±0.8)g/L, (1.1±0.6)g/L, (10.8±0.8)g/L, (34.2±4.8)%, (1.7±0.8), respectively, t=3.324, 2.250, 7.100, 2.506, 2.660, all P<0.05], the IgA and CD4/CD8 in the observation group were higher than those in the control group B[(2.6±0.8)g/L, (1.9±0.7), t=2.021, 2.127, all P<0.05]. The postoperative exhaust time of the observation group, control group A and control group B were (56.4±7.8)h, (78.6±10.4)h, (60.7±10.6)h, respectively, and the postoperative exhaust time of the observation group was significantly shorter than that of the control group A(t=9.323, P<0.05). There was no statistically significant difference in the gastrointestinal symptoms and postoperative complications among the three groups (P>0.05). Conclusion In perioperative period, immunomodulating enteral nutrition has little effect on the nutritional indicators of patients with gastric cancer and the incidence of postoperative complications, but it can improve the immune function.

Objective To study the expression of BRG1 gene in colon cancer and its relationship with histological grade and clinicopathological stages characteristics.Methods The expression of BRG1 -positive cancer cells were detected by immunohistochemistry in 100 cases of colon cancer,and the relationship with histological grade and clinicopathological stages characteristics was analyzed.Results Of the 100 colon cancer specimens analyzed,the positive expression rate was 82.0%.The expression of BRG1 in colon cancer tissue with histological grade and TNM staging was significantly different (χ2 =23.509,P =0.024;χ2 =25.659,P =0.002).The higher the histological grade,the stronger the BRG1 expression in colon cancer tissue.BRG1 expression in advanced colon cancer tissue was significantly enhanced in the early stage.Conclusion The appearance of BRG1 -positive cancer cells is associated with histological grade and clinicopathological stages characteristics.BRG1 might play an important role in the development of colon cancer.

Objective To analyze the clinical efficacy of endovenous laser treatment combined with transilluminated powered phlebectomy for great saphenous varicosity and summarize the experiencein order to achieve better results.Methods From January 2014 to June 2015,45 patients (52 limbs,including 17 males and 28 females,aged 36 to 68 years) diagnosed as great saphenous varicosity received endovenous laser treatment combined with transilluminated powered phlebectomy.Thirty-eight cases was unilateral great saphenous vafcose veins,7 cases was bilateral large saphenous varicose veins.The clinical efficacy was analyzed.Results All cases were performed successfully.The mean operation time was (68.4 ± 15.1) minutes,the average bleeding volume was (23.5 ± 10.7) ml,the number of mean operative incision quantity was (5.8 ± 1.9) and the average hospitalization time was (5.9 ± 1.6) days.All patients had no serious complications.During a mean follow-up time of 22 months (12 to 30 months),only one patient recurred.Conclusions Endovenous laser treatment combined with transilluminated powered phlebectomy for great saphenous varicosity is effective and safe.It also has the advantages of shorter operation time,less bleeding,shorter hospitalization time,small trauma and better cosmetic results.

Objective To investigate the application value of split type tubercle on the surgical treatment of unilateral thyroid benign nodules.Methods 180 cases of unilateral benign thyroid nodules were selected,and they were randomly divided into split type tubercle resection group(group A,n =90) and hemithyroidectomy group(group B,n =90) according to the digital table.The clinical effects were compared in the two groups.Results There was no complication such as hypocalcaemia and postoperative hemorrhage.1 case of group A and 2 cases of group B had transient vocal cord palsy,there was no statistically significant difference (P ＞ 0.05).There were 6 cases postoperative nodule recurrences in group A,and 5 cases in group B during 6 months to 5 years follow-up,there was no statistically significant difference(P ＞0.05).The thyroid stimulating hormone(TSH) levels of the two groups showed no statistically significant difference before operation (P ＞ 0.05).However,the TSH level of group A (2.76 ± 1.34)IU/mL was lower than (4.31 ± 2.01)IU/mL of group B 1 year after operation,and the difference was significant between the two groups (t =9.235,P ＜ 0.05).Conclusion The split type tubercle resection is worthy to properly applied in surgical treatment of unilateral benign thyroid nodules.

Objective To compare the efficacy of endovenous laser treatment combined with transilluminated powered phlebectomy and traditional surgical treatment for great saphenous varicosity. Methods From January 2014 to January 2015,77 patients diagnosed as great saphenous varicosity were enrolled. They were randomly divided into two groups, 37 patients received endovenous laser treatment combined with transilluminated powered phlebectomy and the other 40 patients underwent traditional surgical treatment. The related indicators were compared.Results The mean operation time,average bleeding volume,operative incisionquantity and average hospitalization time of EVLT+ TIPP group were (66.1±14.7) min,(24.4±10.5) ml,5.7±1.7,(5.6±1.4) d respectively,of control group were (84.3±18.5) min,(59.0±15.6) ml,8.0±1.8,(10.1±3.1) d respectively,there were significant differences between the two groups(t =-4.749,-11.460,-5.714;P<0.001) .There were no significant complications in the two groups.In the EVLT+ TIPP group,6 patientsoccurred patsubcutaneous induration, 5 patients occurred subcutaneous hematoma and 7 patients had skinparesthesias.In the traditional operation group,2 cases occurred patsubcutaneous induration,3 cases occurredsubcutaneous hematoma and 2 cases had skin paresthesias.The EVLT+ TIPP group was slightly higher than thetraditional operation group in the complications, but there were no significant differences between them ( P>0.05).During a mean follow?up time of (18±7) months(12 months to 24 months),1 patient recurrence in theEVLT+ TIPP group,2 cases recurrence in the traditional operation group.The recurrence rates of the two groupswere similar,the difference was not significant between them(P=1.000) .Conclusion Endovenous lasertreatment combined with transilluminated powered phlebectomy for great saphenous varicosity is effective andsafe.It also has the advanta and better cosmetic results.