Abstract Background: The study aims to investigate the expression level of Thrombospondin 2 (TSP2) in Gastric Cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis. Methods: The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyze the mRNA expression level of TSP2 in GC. The Kaplan-Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. The expression level of TSP2 was analyzed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between clinicopathological characteristics and prognosis of GC patients. Next, the relationship between clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiment was used to evaluate the effect of TSP2 on the invasion and migration of HGC27 and AGS cells. Results: Compared with normal tissues, the expression of TSP2 mRNA in GC was significantly up-regulated, and it was closely related to the clinical stage of GC. The high expression of TSP2 significantly affected the OS, FP and PPS of patients with GC. Among them, the expression level of TSP2 did not affect the prognosis of patients with GC in N0 subgroup, but significantly affected the prognosis of patients with GC in N (1+2+3)subgroup. The protein expression level of TSP2 in GC tissue was significantly higher than in normal tissues (P<0.01). The overall survival (OS) rate of patients with high TSP2 expression was lower than the low TSP2 expression group ( P =0.013). Knockdown of TSP2 can significantly inhibit the growth of GC cells. Proliferation, migration, invasion ability, and TSP2 expression level significantly correlate with mismatch repair genes such as PMS2, MSH6, MSH2, and MLH1 ( P <0.05). Conclusion : The expression of TSP2 in GC is significantly increased, closely related to the metastasis and mismatch repair process of GC patients and affected GC patients' prognosis. It is a potential marker and treatment target for the prognosis of GC patients.
The engine casing components operate in high-temperature and high-pressure environments. Process holes are drilled when defects occur. Welding is employed in the repair of process holes as a process for permanently joining materials. The traditional welding method relies on padding, which results in poor back formation of process holes. Additionally, the shape of the process holes imposes high requirements on the size of the droplet transition. The conventional approach of adjusting a welding current makes it difficult to achieve stable droplet transition and precise formation of small holes. It poses a challenge for the robotic welding process. To deal with this problem, the influence of the high-frequency vibration GTAW process on the directional transition of molten droplets is studied. The molten droplet directional transition process is developed. The impact of vibration energy on the molten pool is reduced. Welding repair experiments for process holes are successfully conducted. When the frequency is 3 Hz, the transition of droplets changes from a continuous one-droplet transition to a discontinuous liquid bridge transition. The residual height and mechanical properties of the repaired area are tested. The experimental results indicated that the residual height after dual-side repair is ≤0.7 mm. The X-ray and fluorescent penetration tests have a 100% first-pass qualification rate. The repaired area demonstrates a hardness of 480 HV and a room-temperature tensile strength of 1069 MPa. The repair process requirements for the casing are met.
To investigate the feasibility and efficacy of laparoscopic Roux-en-Y gastric bypass(LRYGB) for super obesity(BMI≥50 kg/m(2)).Clinical data of 42 patients undergoing LRYGB in the First Affiliated Hospital of Jinan University between 2004 and 2008 were analyzed retrospectively.All the LRYGB procedures were successfully performed with no conversion to open surgery. Average operation time was 145.1 minutes, volume of blood loss during the surgery was 25.0 ml, and length of postoperative hospital stay was 9.9 days. The cases were followed up for 1 month to 30 months. Body weight and BMI decreased significantly 1 month after the operation and reached a minimum level after 2 years then became stable while excess body weight loss rate(EWL) increased(P<0.05). All the obese-related symptoms were relieved significantly. Four cases(9.5%) showed complications during perioperative period including 1 case of respiratory failure, 2 cases of gastrojejunal anastomotic bleeding, 1 case of umbilical wound infection, and 11 developed long-term complications. All of them were cured by conservative treatment.Treatment of super obesity by LRYGB is feasible with significant short-term results. But due to the difficulty of the operation and postoperative complications, comprehensive treatment from experienced bariatric surgical team is needed. The long-term outcome needs for further observation.
Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression.However, the prognostic role of TLS in various tumors remains controversial.This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors.Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020.Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors.Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed.High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 -0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 -0.79, P = 0.0001).Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 -0.57, P < 0.0001).However, there was no relationship between TLS expression and DFS.Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs).Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer.Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse.Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor.Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.
Background: Long noncoding RNA KCNQ1 opposite strand/antisense transcript 1 (lncRNA KCNQ1OT1) is abnormally expressed in various solid tumors.The purpose of this study was to explore the prognostic value and potential functional role of lncRNA KCNQ1OT1 across cancers.Methods: We performed a meta-analysis of published literature to evaluate the prognostic value of lncRNA KCNQ1OT1 across cancers.Verification, functional analysis, and genomic variation analysis were performed using the GEPIA, TIMER, and LnCeVar databases.According to the immune cell infiltration level, we established a prognostic model of lncRNA KCNQ1OT1 expression using public datasets of TIMER.We used quantitative real-time polymerase chain reaction (RT-qPCR) and western blot to detect the expression levels of lncRNA KCNQ1OT1 and the CD155 protein in colorectal cancer (CRC) tissues and cell lines.Then, a lncRNA KCNQ1OT1-knockdown cell line was cocultured to explore the role of lncRNA KCNQ1OT1 and CD155 in the T cell response by flow cytometric analysis.Results: Our results showed that the high expression of lncRNA KCNQ1OT1 was significantly related to poor overall survival across cancers, especially CRC.Interestingly, we found that COAD patients with high lncRNA KCNQ1OT1 expression and high CD8 + T cell infiltration levels had a worse prognosis than those with low lncRNA KCNQ1OT1 expression and high CD8 + T cell infiltration levels.Moreover, lncRNA KCNQ1OT1 and CD155 showed significantly higher expression in CRC tissue than in normal tissue, and lncRNA KCNQ1OT1 expression was positively correlated with CD155 expression in CRC.Finally, knockdown of lncRNA KCNQ1OT1 reduced CD155 expression in HCT116 and SW620 cells and enhanced the immune response in coculture with CD8 + T cells.Conclusions: High lncRNA KCNQ1OT1 expression is significantly correlated with poor prognosis of CRC patients and mediates the CD8 + T cell response in CRC.These findings indicate that lncRNA KCNQ1OT1 is a prognostic biomarker and potential immune therapeutic target for enhancing the CD8 + T cell response in CRC.
Peptidyl arginine deiminase 1 (PADI1) catalyzes protein citrullination and has a role in regulating immune responses. The tumor immune microenvironment has been reported to be important in colorectal cancer (CRC), which was correlated with the ability of CRC patients to benefit from immunotherapy. However, there is a lack of molecular markers for matching CRC immunotherapy. Previously, single-gene risk models have only considered the effect of individual genes on intrinsic tumor properties, ignoring the role of genes and their co-expressed genes as a whole. In this study, we analyzed the differential expression of PADI1 in colorectal cancer (CRC). We found that PADI1 was highly expressed in CRC. Subgroup survival analysis revealed a prognostic survival difference for PADI1 in CRC patients aged less than 65 years, male, T stage, N0, M0, and stage I-II (p < 0.05). In addition, we analyzed the functions and signaling pathways associated with PADI1 in CRC and found that it was highly enriched in several immune-related functions and pathways. Then, a set of PADI1 co-expressed genes (PCGs) risk-prognosis scores was developed with PADI1 as the core, which could accurately predict the prognosis of CRC (p < 0.05). PCGs risk score can be an independent prognostic factor for CRC. A new set of Norman plot models were developed for clinical characteristics with age, sex, and TNM stage, which can accurately predict CRC 1, 3, and 5 years survival, and calibration curves and decision curve analysis (DCA) validated the accuracy of the models. The risk score assessed the immune microenvironment of CRC and found that the immune score was higher in the low-risk group, and CD4+ T cells, helper T cells, and eosinophils were more infiltrated in the low-risk group (p < 0.05). Immunotherapy efficacy was better in the low-risk group (p < 0.05). The underlying mechanism may be that the high-risk group of PCGs was enriched in some pathways that promote immune escape and immune dysfunction. In conclusion, PCGs may better predict CRC prognosis and immunotherapeutic response.
Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer. The recognition of antigens by immune cells is a crucial step in tumor-specific killing, and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells, making them an attractive therapeutic target. Currently, neoantigens find utility in various domains, primarily in the realm of neoantigen vaccines such as DC vaccines, nucleic acid vaccines, and synthetic long peptide vaccines. Additionally, they hold promise in adoptive cell therapy, encompassing tumor-infiltrating cells, T cell receptors, and chimeric antigen receptors which are expressed by genetically modified T cells. In this review, we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens, discussed the potential of neoantigen burden as an immune checkpoint in clinical settings. With the aid of state-of-the-art sequencing and bioinformatics technologies, together with significant advancements in artificial intelligence, we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy, from screening to clinical application.
To compare long term effects of two bariatric procedures for Chinese type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) of 28-35 kg/m(2).Sixty four T2DM patients with Glycated hemoglobin A1c (HbA1c) ≧ 7.0 % were randomly assigned to receive laparoscopic sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedure. Weight, percentage of excess weight loss (%EWL), BMI, waist circumference, HbA1c, fasting blood glucose (FBG), and C-peptide were measured. Serum lipid levels were also measured during three-year postoperative follow-up visits.Fifty five patients completed the 36-month follow-up. Both groups had similar baseline anthropometric and biochemical measures. At the end point, 22 patients (78.6 %) in SG group and 23 patients (85.2 %) in RYGB group achieved complete remission of diabetes mellitus with HbA1c < 6.0 % (P = 0.525) and without taking diabetic medications, and 25 patients in each group (89.3 % vs. 92.6 %) gained successful treatment of diabetes with HbA1c≦6.5 % (P = 0.100). Change in HbA1c, FBG and C peptide were comparable in the two groups. The RYGB group had significantly greater weight loss than the SG group [percentage of total weight loss (%TWL) of 31.0 % vs. 27.1 % (P = 0.049), %EWL of 92.3 % vs. 81.9 % (P = 0.003), and change in BMI of 11.0 vs. 9.1 kg/m(2)(P = 0.017), respectively]. Serum lipids in each group were also greatly improved.In this three-year study, SG had similar positive effects on diabetes and dyslipidemia compared to RYGB in Chinese T2DM patients with BMI of 28-35 kg/m(2). Longer term follow-ups and larger sample studies are needed to confirm these outcomes, however.
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