Application of hand-sewn esophagojejunostomy in laparoscopic total gastrectomy.

OBJECTIVE: To investigate the clinical efficacy and prognostic implication of hand-sewn anastomosis in laparoscopic total gastrectomy (LTG). METHODS: Retrospective analysis is adopted to the clinicopathologic data of 112 patients with gastric cancer (GC) who went through LTG in the Department of General Surgery, the Second Affiliated Hospital of Anhui Medical University between October 2020 and October 2022. Among them, 60 individuals receiving medical care were split into the hand-sewn anastomosis group (Group H, N = 60); while, 52 individuals were split into the circular stapler anastomosis group (Group C, N = 52) The clinical efficacy and prognostic conditions of hand-sewn anastomosis are compared with those of circular stapler anastomosis in the application of LTG. RESULTS: The analysis results indicated that no notable difference was observed in intraoperative bleeding volume, time to first flatus (TFF), postoperative hospitalization duration and postoperative complications among the two groups (P > 0.05). Group H had shorter esophagojejunal anastomosis duration (20.0 min vs. 35.0 min) and surgery duration (252.6 ± 19.4 min vs. 265.9 ± 19.8 min), smaller incisions (5.0 cm vs. 10.5 cm), and lower hospitalization costs (58415.0 CNY vs. 63382.5 CNY) compared to Group C (P < 0.05). CONCLUSION: The clinical efficacy and the postoperative complications of hand-sewn esophagojejunostomy are basically equivalent in comparison to the circular stapler anastomosis in the application of LTG. Its advantage lies in shorter esophagojejunal anastomosis duration, shorter surgery duration, smaller incisions, lower hospitalization costs and wider adaptability of the location of the tumor.

Lysine demethylase 5C inhibits transcription of prefoldin subunit 5 to activate c-Myc signal transduction and colorectal cancer progression.

BACKGROUND: Lysine demethylase 5C (KDM5C) has been implicated in the development of several human cancers. This study aims to investigate the role of KDM5C in the progression of colorectal cancer (CRC) and explore the associated molecular mechanism. METHODS: Bioinformatics tools were employed to predict the target genes of KDM5C in CRC. The expression levels of KDM5C and prefoldin subunit 5 (PFDN5) in CRC cells were determined by RT-qPCR and western blot assays. The interaction between KDM5C, H3K4me3, and PFDN5 was validated by chromatin immunoprecipitation. Expression and prognostic values of KDM5C and PFDN5 in CRC were analyzed in a cohort of 72 patients. The function of KDM5C/PFDN5 in c-Myc signal transduction was analyzed by luciferase assay. Silencing of KDM5C and PFDN5 was induced in CRC cell lines to analyze the cell malignant phenotype in vitro and tumorigenic activity in nude mice. RESULTS: KDM5C exhibited high expression, while PFDN5 displayed low expression in CRC cells and clinical CRC samples. High KDM5C levels correlated with poor survival and unfavorable clinical presentation, whereas elevated PFDN5 correlated with improved patient outcomes. KDM5C mediated demethylation of H3K4me3 on the PFDN5 promoter, suppressing its transcription and thereby enhancing the transcriptional activity of c-Myc. KDM5C knockdown in CRC cells suppressed cell proliferation, migration and invasion, epithelial-mesenchymal transition, and tumorigenic activity while increasing autophagy and apoptosis rates. However, the malignant behavior of cells was restored by the further silencing of PFDN5. CONCLUSION: This study demonstrates that KDM5C inhibits PFDN5 transcription, thereby activating c-Myc signal transduction and promoting CRC progression.

Efficacy of lidocaine wet compress combined with red-light irradiation for chronic wounds.

BACKGROUND: Chronic wounds that fail to progress through normal phases of healing present a significant healthcare burden owing to prolonged treatment and associated costs. Traditional wound care typically involves regular dressing changes, which can be painful. Recent approaches have explored the use of lidocaine to manage pain and red-light irradiation (RLI), known for its anti-inflammatory and cell proliferation effects, to potentially enhance wound healing. AIM: To investigate the therapeutic efficacy of lidocaine wet compression (LWC) combined with RLI for chronic wounds. METHODS: We enrolled 150 patients with chronic wounds from the Wound and Ostomy Outpatient Clinic of the Second Hospital of Anhui Medical University from April to September 2022. The wounds were treated with dressing changes. The patients were randomly assigned to the control and experimental groups using a random number table and given the same first dressing change (2% LWC for 5 min and routine dressing change). From the second dressing change, in addition to 2% LWC for 5 min and routine dressing change, the experimental group received RLI, whereas the control group continued to receive the same LWC and dressing change. The first and second dressing changes were performed on days 1 and 2, respectively. The third dressing change was performed 3 d after the second change. The frequency of subsequent dressing changes was determined based on wound exudation and pain. Pain during the first three dressing changes was evaluated in both groups. The average number of dressing changes within 28 d and the degree of wound healing on day 28 were also recorded. RESULTS: During the initial dressing change, no noticeable differences were observed in the pain levels experienced by the two groups, indicating similar pain tolerance. However, during the second and third dressing changes, the experimental group reported significantly less pain than the control group. Furthermore, over 28 d, the experimental group required fewer dressing changes than the control group. CONCLUSION: Notably, the effectiveness of wound healing on the 28th day was significantly higher in the experimental group than that of in the control group. The combination of LWC and RLI was effective in reducing early-stage pain, promoting wound healing, decreasing the frequency of dressing changes, and enhancing patients' overall quality of life with chronic wounds.

SUMO1-modified DNA methyltransferase 1 induces DNA hypermethylation of VWC2 in the development of colorectal cancer.

Aberrant DNA methylation of genes is closely linked to many aspects of tumor development. This study focuses on the effect of DNA hypermethylation of von Willebrand factor C domain containing 2 (VWC2) on colorectal cancer (CRC) progression and the underpinning mechanism. According to data in the bioinformatic systems, VWC2 had the highest degree of DNA methylation in colonic adenocarcinoma, and it showed DNA hypermethylation in rectal adenocarcinoma as well. CRC and the para-tumorous tissues were collected from 86 patients. VWC2 was expressed at low levels in CRC samples and inversely correlated with tumor stage and tumor biomarker expression. DNA hypermethylation and reduced expression of VWC2 were also detected in CRC cell lines HCT-116 and HT29. VWC2 overexpression suppressed the malignant growth of cells in vitro and in vivo. Co-immunoprecipitation and western blot assays showed that small ubiquitin-like modifier 1 (SUMO1) mediated SUMOylation of DNA methyltransferase 1 (DNMT1) and strengthened its protein stability, which promoted DNA methylation and suppression of the VWC2 gene. In summary, this study demonstrates that SUMO1-mediated activation of DNMT1 induces DNA methylation and downregulation of VWC2 in CRC to augment cancer development.

The Number of Intraoperative Intestinal Venous Circulating Tumor Cells Is a Prognostic Factor for Colorectal Cancer Patients.

Purpose: To assess the association between intestinal venous blood (IVB) circulating tumor cells (CTCs) and clinicopathological parameters in stage I-III colorectal cancer (CRC) patients. Methods: Participants were retrospectively retrieved, who were admitted to our hospital or took annual physical exams between December 1, 2015 and December 31, 2018. A negative enrichment-immunofluorescence in situ hybridization (NE-imFISH) technique was used to isolate and identify CTCs. Receiver operating characteristic (ROC) curves and Youden index values were used to determine the critical CTC cutoff value for the diagnosis of CRC. Kaplan-Meier and log-rank methods were used to conduct survival analyses, and multivariate Cox regression analyses were employed for multivariate corrections to comprehensively evaluate the value of CTCs in the diagnosis of CRC. Relationships between IVB CTCs, clinicopathological parameters, and prognosis were then analyzed based upon patient postoperative follow-up data. Results: In total, we retrieved 282 patients including 48 healthy controls, 72 patients with benign colorectal tumors, and 162 CRC patients. CRC patients exhibited significantly higher numbers of CTCs relative to control patients or those with benign disease. CTC numbers in CRC patient peripheral blood (PB) and IVB were closely associated with tumor node metastasis (TNM) staging (P < 0.01), carbohydrate antigen-125 (CA-125) levels (P < 0.001), and KRAS (Kirsten rat sarcoma virus oncogene) mutation status (P < 0.001). The disease-free survival (DFS) of patients in the CTC-negative group was significantly longer than that of patients in the CTC-positive group (24.60 ± 13.31 months vs. 18.70 ± 10.19 months, P < 0.05), with the same being true with respect to their overall survival (OS) (30.60 ± 12.44 months vs. 35.25 ± 11.57 months, P < 0.05). A multivariate analysis revealed that the detection ≥2 CTCs/3.2 ml was independently associated with poorer DFS and OS. CTC counts were independently predictive of CRC patients TNM staging, CA-125, and KRAS mutation status in both univariate and multivariate Cox proportional hazards regression analyses. Conclusion: CTCs are valuable biomarkers that can be monitored to predict CRC patient disease progression.

Mucin 16 Promotes Colorectal Cancer Development and Progression Through Activation of Janus Kinase 2.

BACKGROUND: Mucin 16 (MUC16), a cell surface-associated mucin, has been implicated to be upregulated in a large repertoire of malignances. However, its function in the pathogenesis of colorectal cancer (CRC) is unknown. AIMS: Here, we explored the regulatory role of MUC16 in CRC. METHODS: First, tumor and paracancerous tissues, and serum samples from 162 CRC patients, peripheral blood samples from 48 healthy volunteers and 72 benign colorectal patients were collected. The correlation between the MUC16 expression and the clinical phenotypes of the patients was analyzed. Subsequently, HCT116 and SW480 cells with deletion of MUC16 were established to detect changes in the growth and metastatic capacities of CRC cells. The genes with the highest correlation with MUC16 were predicted by bioinformatics, and their binding relationships were detected by Co-IP and double-labeled immunofluorescence, followed by functional rescue experiments. RESULTS: Overexpression of MUC16 in CRC patients was positively correlated with serum biomarkers and poor prognosis of patients. It was demonstrated by in vitro and in vivo experiments that knocking-down the expression of MUC16 could significantly inhibit the growth and metastasis of CRC cells. MUC16 activated janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) by interacting with JAK2. Further overexpression of JAK2 in cells with poor expression of MUC16 revealed a significant increase in the proliferative and metastatic capacities of CRC cells. CONCLUSIONS: MUC16 contributes to the development and progression of CRC by binding to JAK2, thereby promoting phosphorylation of JAK2 and further activating STAT3 phosphorylation.

Upregulation lnc-NEAT1 contributes to colorectal cancer progression through sponging miR-486-5p and activating NR4A1/Wnt/ß-catenin pathway.

Colorectal cancer is a major public health problem and fourth guiding cause of cancer-induced mortality worldwide. The five-year survival rate for patients with colorectal cancer remains poor, and almost half of colorectal cancer patients present recurrence and die within five years. The increasing studies showed that long non-coding RNA (lncRNA) was involved in colorectal cancer. Therefore, this study was used to explore molecular mechanisms of nuclear paraspeckle assembly transcript 1 (NEAT1) in colorectal cancer. The real-time quantitative polymerase chain reaction (RT-qPCR) was employed to estimate the expression levels of NEAT1, Nuclear receptor 4 A1 (NR4A1), and miR-486-5p in colorectal cancer tissues and cells. Kaplan-Meier curve was conducted to analyze relationship between survival time of colorectal cancer patients and level of NEAT1. The protein levels of NR4A1, ß-catenin, c-Myc, and cyclinD1 were assessed with western blot assay. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) and flow cytometry assays were performed to evaluate proliferation and apoptosis of colorectal cancer cells, respectively. The migration and invasion abilities of cells were examined by transwell assay. The relationship between miR-486-5p and NEAT1 or NR4A1 was confirmed by dual-luciferase reporter assay. We found NEAT1 and NR4A1 were highly expressed in colorectal cancer tissues and cell lines compared with controls. Loss-functional experiments revealed that knockdown of NEAT1 or NR4A1 repressed proliferation and motility, while inducing apoptosis of colorectal cancer cells. The gain of NR4A1 could abolish NEAT1 silencing-induced effects in colorectal cancer cells. In addition, NEAT1 contributed to colorectal cancer progression through mediating NR4A1/Wnt/ß-catenin signaling pathway. In conclusion, NEAT1 stimulated colorectal cancer progression via acting as competing endogenous RNA to sponge miR-486-5p and regulate NR4A1/Wnt/ß-catenin signaling pathway.

Comprehensive Analysis of Alternative Splicing Signature in Gastric Cancer Prognosis Based on The Cancer Genome Atlas (TCGA) and SpliceSeq Databases.

BACKGROUND Increasing evidence suggests that the alternative splicing (AS) signature plays a role in the carcinogenesis and prognosis of various cancers. However, the prognostic role of AS in gastric cancer is not clear and needs to be clarified. MATERIAL AND METHODS To identify the differentially expressed AS (DEAS) events, we performed a differential expression analysis between normal and tumor tissue. The DEAS event was further applied to construct a prognostic signature by performing univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) analysis. The Kaplan-Meier curve analysis and receiver operating characteristic curve (ROC) analysis were used to evaluate the prognostic value of the AS signature. In addition, the network of the splicing events with splicing factors was constructed using the Cytoscape software. RESULTS A total of 30 005 alternative splicing (AS) events with 372 patients were retrieved from the SpliceSeq database and TCGA database. By performing differential expression analysis, a total of 419 alternative splicing events were screened out, including 56 upregulated and 363 downregulated. We further constructed an AS-related prognostic signature by conducting a series bioinformatics analyses. Moreover, we identified that the AS signature could serve as an independent predictor for the prognosis of GC. We also found that AS signature had a more robust and precise efficacy for prognostic prediction in GC patients. Interestingly, the areas under 3- and 5-year survival curves are similar, both of which are greater than 1-year survival curve, suggesting that the long-term predictive accuracy of our prognostic model built upon AS signature is superior. CONCLUSIONS We performed a comprehensive analysis of overall prognostic-associated AS events concerning GC and constructed a prognostic model to predict the long-term prognostic survival outcomes in GC patients. We also developed a network of splicing events with splicing factors to reveal new potential molecular diagnostic biomarkers and therapeutic targets for GC patients.

MicroRNA-429 sensitizes pancreatic cancer cells to gemcitabine through regulation of PDCD4.

One of the features for pancreatic cancer is that it is often resistant to chemotherapy treatment, which is one of the major hindrances in the treatment of this malignancy. Previous studies indicated that the microRNAs (miRNAs) could mediate resistance of tumor cells to chemotherapy drug in the cancer progression. In the present study, we are aimed to examine whether microRNA-429 was involved in mediating the chemo-resistance of pancreatic cancer cells to gemcitabine. Firstly, a gemcitabine-resistant pancreatic cancer cell line (SW1990/GZ) derived from cell line (SW1990) was constructed and found to possess a decreased expression of miR-429 when it is compared to the original cell line. Ectopic expression of miR-429 in SW1990/GZ increased the cellular sensibility to the treatment of gemcitabine, which is coincided with increased expression of PDCD4. As a tumor suppressor, we found that PDCD4 knockdown in SW1990/GZ cells increased its own chemo-resistance to GZ, which indicates PDCD4 also play a regulative role on the GZ-resistance in the pancreatic cancer. To further confirm the function of miR-429 and PDCD4 in gemcitabine-resistant pancreatic cancer, a xenograft nude mouse model was utilized to examine whether miR-429 can restore treatment response of gemcitabine in gemcitabine-resistant xenografts, while protein levels of PDCD4 were up-regulated. Together with those results, these findings collectively provided that miR-429 could enhancer GZ sensitivity via regulation of PDCD4 expression in pancreatic cancer cells, which may offer a novel therapeutic target for the chemotherapy resistance in pancreatic cancer.