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N6-methyladenosine (m6A) is the most prevalent RNA modification and is associated with various biological processes. Proteins that function as readers and writers of m6A modifications have been shown to play critical roles in human malignancies. Here, we identified KH-type splicing regulatory protein (KHSRP) as an m6A binding protein that contributes to the progression of pancreatic ductal adenocarcinoma (PDAC). High KHSRP levels were detected in PDAC and predicted poor patient survival. KHSRP deficiency suppressed PDAC growth and metastasis in vivo. Mechanistically, KHSRP recognized and stabilized FAK pathway mRNAs, including MET, ITGAV and ITGB1, in an m6A-dependent manner, which led to activation of downstream FAK signaling that promoted PDAC progression. Targeting KHSRP with a PROTAC showed promising tumor suppressive effects in mouse models, leading to prolonged survival. Together, these findings indicate that KHSRP mediates FAK pathway activation in an m6A-dependent manner to support PDAC growth and metastasis, highlighting the potential of KHSRP as a therapeutic target in pancreatic cancer.

Cancer metastasis is a symptom of adverse prognosis, a prime origin of therapy failure, and a lethal challenge for cancer patients. N 6 -methyladenosine (m 6 A), the most prevailing modification in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) of higher eukaryotes, has attracted increasing attention. Growing studies have verified the pivotal roles of m 6 A methylation in controlling mRNAs and ncRNAs in diverse physiological processes. Remarkably, recent findings have showed that aberrant methylation of m 6 A-related RNAs could influence cancer metastasis. In this review, we illuminate how m 6 A modifiers act on mRNAs and ncRNAs and modulate metastasis in several cancers, and put forward the clinical application prospects of m 6 A methylation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dang, Shao, Zhou, Chen, Guo, Wang, Liu, Kan, Yuan and Sun.)

Yes-associated protein 1 (YAP1) exerts significant effects in various malignancies. However, the oncogenic role of YAP1 remains controversial, and the mechanism by which YAP1 regulates non-coding RNAs is still largely unknown. The present study aimed to assess the effect of YAP1 on the malignant behaviors of colorectal carcinoma (CRC) and explore the underlying regulatory mechanism of the YAP1-MALAT1-miR-126-5p axis. YAP1 was highly expressed in CRC tissues as assessed by GSE20916 and its expression was negatively correlated with overall survival in 83 CRC cases. Meanwhile, YAP1 promoted proliferation, invasion, and migration in colon cancer cells, in vitro and in vivo. MALAT1 was obviously expressed, with differential expression of 11 lncRNAs in HCT116 cells after transfection with siYAP1 or si-Ctl. Based on bioinformatics prediction, immunoprecipitation (IP), and chromatin immunoprecipitation (ChIP), the interaction of YAP1 with TCF4/β-catenin was regulated by MALAT1. Bioinformatics prediction, dual luciferase assay, RNA-IP, and RNA pull-down assay demonstrated that YAP1-induced MALAT1 promoted the expression of metastasis-associated molecules such as VEGFA, SLUG, and TWIST, by sponging miR-126-5p in CRC. These findings indicated that the YAP1-MALAT1-miR-126-5p axis could control angiogenesis and epithelial-mesenchymal transition in CRC, providing potential biomarkers and therapeutic targets for CRC.

Objective: To compare the clinical efficacy of robotic and laparoscopic radical surgery in the treatment of middle-low rectal cancers., Methods: From January 2015 to March 2016, intra-operative and postoperative follow-up data of 30 patients with middle-low rectal cancers who underwent robotic radical resection(robot group) and 32 patients with middle-low rectal cancers who underwent laparoscopic radical resection (laparoscopy group)n in our department were retrospectively collected. The distance from cancer to anal margin was less than 10 cm in both two groups and advanced rectal cancers were confirmed by preoperative colonoscopy biopsy. Associated data were compared between two groups., Results: There were 13 males and 17 females in robot group with age of 27 to 85 (mean 59.7) years, disease course of 3 to 12 (mean 6.2) months and clinical stage T2-3N0-1. There were 16 males and 16 females in laparoscopic group with age of 32 to 79 (mean 60.3) years, disease course of 2 to 10(mean 5.9) months and clinical stage T2-3N0-1. The baseline data of two groups were not significantly different (all P>0.05). All the patients in two groups completed operations successfully without conversion to open operation. Compared with laparoscopic group, the blood loss was less [(100.3±43.7) ml vs. (150.3±68.2) ml, t=3.413, P=0.001], the first flatus time [(49.3±12.4) h vs. (58.6±12.5) h, t=2.838, P=0.006] and urinary catheter removal time [(3.0±0.7) d vs. (4.8±0.9) d, t=5.491, P=0.000] were shorter, while the operation time [(217.3±57.8) min vs. (187.9±23.1) min, t=2.772, P=0.009] was longer in robot group. No cancer tissue was observed in resection margin of two groups. Number of harvested lymph node per case (15.2±7.4 vs. 13.9±4.9, t=-0.764, P=0.448), distance from anal margin to tumor distal edge [(7±3) cm vs. (6.5±3) cm, t=-1.952, P=0.056] and postoperative hospital stay [(13.6±1.3) d vs. (13.8±1.8) d, t=0.925, P=0.359] were not significantly different between two groups. No serious complications occurred in two groups during intra-operative and postoperative period. During following up of 3 to 12 (average 8.7) months, 1 case of anastomotic fistula occurred in each group and was cured by conservative treatment without significant difference [3.3%(1/30) vs. 3.1%(1/32), P=1.000]. No sexual dysfunction was found in either groups. Two cases in laparoscopic group presented relapse and metastasis, but no recurrence and metastasis was observed in robot group. There was no death in two groups., Conclusion: Robotic radical surgery in the treatment of middle-low rectal cancers is safe and effective with the advantages of less trauma, less bleeding, rapid recovery of intestinal function and urinary function.

Objective: To explore the efficacy and safety of laparoscopic tunnel-like peri-anterior superior iliac spine suspension(L-TASISS) or combined with stapled transanal rectal resection (STARR) in the treatment of pelvic organ prolapse (POP) with outlet obstructive constipation (OOC)., Methods: A total of 119 POP patients complicated with OOC( II( to IIII( stage evaluated by POP-Q) received L-TASISS or combined with STARR in the First Affiliated Hospital of Zhengzhou University from August 2010 to January 2015. Clinical and follow-up data of these patients were analyzed retrospectively and compared before and after operation., Results: Among 119 cases, 51 cases(42.9%) underwent L-TASISS alone, and 68 cases (57.1%) received L-TASISS combined with STARR. All the 119 patients were successfully operated without conversion to open surgery. The operation time was (67.8±10.9) minutes, the intra-operative blood loss was (10.3±3.8) ml, the indwelling catheter time was (3.6±1.1) days, and hospital stay was (5.1±1.8) days. One month after operation, abdominal wall pain or stress occurred in 15 cases, of whom 3 cases were improved by local block injection, 1 case by incision stitches release, the rest ameliorated spontaneously within 3 months after surgery. No potential ureterostenosis, hydroureterosis, internal iliac vascular thrombosis resulting from compression of the mesh and other complications related to the mesh were found. One year after operation, all the patients were followed up. The OOC remission rate was 78.2%(93/119), of whom 76 cases were satisfied and 17 patients were completely satisfied. One case(0.8%) with stress urinary incontinence did not improve. Fifteen cases(12.6%) with algopareunia or dyspareunia did not achieve remission, but there was no new algopareunia or dyspareunia case. Eleven patients (9.2%) presented recurrence of symptoms, of whom 9 cases(7.6%) complained of sensation of incomplete evacuation. Two cases(1.7%) were graded as POP-Q II(, and 1 case (0.8%) as POP-Q III( after surgery. Constipation Score of all the patients was 1.4±0.9 (compared to 7.8±3.6 preoperatively) according to Rome III( criteria. Enterocele occurred in 53 cases (44.5%) preoperatively corresponded with only 1 case (0.8%) after operation (χ(2)=64.77, P=0.000). One hundred and six cases (86.6%) with defecation difficulties and 87 cases (73.1%) with sensation of incomplete evacuation before operation were significantly improved after surgery, corresponding with 7(5.9%) and 9 (7.6%) symptomatic cases respectively (χ(2)=155.78, P=0.000). Three cases (2.5%) with preoperative fecal incontinence symptoms were improved after operation as well., Conclusion: The procedure of L-TASISS or combined with STARR for POP patients with OCC has good short-term efficacy, and is safe and feasible.

Objective: To explore the clinical value of the radical nerve dissection (RND) for the carcinoma of head of pancreas (CHP)., Methods: The clinical and pathological data of 30 CHP patients who underwent RND in our hospital were retrospectively analyzed, with an attempt to explore the safety and short-term efficacy of this procedure., Results: Among these 30 patients, the operative time was (351±61) min, the intra-operative blood loss was 350 (range, 300-600) mL, and the grades B and C pancreatic fistula was 23.33%. During the follow-up (range, 2-30 months; median: 17 months), the 1-year survival rate was 63.33% and the 1-year disease-free survival rate was 56.67%. Among the 23 patients (76.66%) with positive extra-pancreatic perineural invasion (PNI), the 1-year casefatality rate was 34.78%, which was not significantly different from that (28.57%) of patients with negative PNI (P=0.760)., Conclusions: Our results suggested potential advantages of RND in the fields of surgery-associated risk and prognosis compared with the Whipple operation in the treatment of CHP. Due to the low sample size of this study, further well-designed research of large sample size is needed., Competing Interests: The authors have no conflicts of interest to declare.

Purpose: This study was designed to detect the expression of epidermal growth factor receptor (EGFR) in tumor specimens of patients with colorectal cancer (CRC); moreover, the relationship between EGFR expression and clinical factors as well as prognosis were analyzed to provide a basis for individualized treatment of CRC., Methods: This study used paraffin-embedded tumor specimens of 70 CRC patients who were treated with cetuximab. Immunohistochemistry (IHC) was used to detect the expression of EGFR in CRC tumor specimens. The patient clinical features and treatment administered were recorded and then, the therapeutic effect of cetuximab was evaluated. Progression-free survival (PFS) and overall survival (OS) were assessed., Results: The positive expression rate of EGFR was 64% (45/70), while 18 patients had negative expression. Twenty-two cases had weak positive expression, 15 cases positive expression and another 15 strongly positive expression. Of 70 specimens, 27 (38.6%) had high EGFR expression belonging to 20 (50%) males and 7 (23%) females (p<0.05). However, age, Karnofsky performance status (KPS), tumor site, grade of differentiation and clinical stage showed no significant difference in relation to EGFR expression (p>0.05). No patient achieved complete remission (CR), 15 (21.4%) had partial remission (PR), 12 (17.1%) were in stable state (SD) and 40 (57.1%) patients had disease progression (PD). Disease control rate (DCR) was 39.02% (16/41) in the group with low EGFR expression and 48.28% (14/29) in the group with high EGFR expression (p>0.05)., Conclusion: EGFR expression in CRC tissue is correlated with patient gender. In the group with higher EGFR expression, the effectiveness of cetuximab was significantly higher than that in the low EGFR expression group, indicating correlation between the high expression of EGFR and the short-term effect of cetuximab.

As a topical hemostatic agent, thrombin has wide application for many surgical treatments. However, native thrombin always suffers from its physical and chemical instabilities. In this work, a nanocomplexation strategy was developed for modifying the stability and hemostatic efficacy of thrombin, in which a water-soluble cationic amylose derivative containing poly(l-lysine) dendrons was prepared by a click reaction and then used to complex thrombin in an aqueous system. For resultant thrombin nanocomplexes, their morphology and particle size distribution were investigated. Their stabilities were studied in terms of activity retention percentages under different storage time, pH values, and illumination time. In addition, their ability to achieve in vitro fibrinogen and blood coagulation were evaluated. Via a rat hepatic hemorrhage model and a rat iliac artery hemorrhage model, these thrombin nanocomplexes were confirmed to have good tissue biocompatibility and in vivo hemostatic effectiveness.