OBJECTIVE/BACKGROUND:The RNPLS-01 trial aimed to evaluate the efficacy and safety of ramucirumab (a VEGFR2 antagonist) combined with nab-paclitaxel, lobaplatin, and S-1 (RNPLS group) versus nab-paclitaxel, lobaplatin, and S-1 alone (NPLS group) in neoadjuvant therapy for advanced gastric cancer (GC), as part of the RNPLS-01 prospective randomized controlled trial. METHODS AND ANALYSIS:RNPLS-01 trial enrolled 140 patients with advanced GC across two cohorts (neoadjuvant therapy: n = 70; conversion therapy: n = 70). This report focuses on the neoadjuvant cohort where patients were randomized 1:1 to receive either RNPLS (n = 35) or NPLS (n = 35). Primary endpoint was pathological complete response (pCR). Secondary endpoints included R0 resection rate, objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS:The RNPLS group demonstrated significant improvements in post-operative T stage ( P = 0.008), N stage ( P = 0.001), and AJCC (American Joint Committee on Cancer) clinical stage ( P = 0.003) compared to controls. The RNPLS group demonstrated significantly higher pCR rates compared to the NPLS group (22.9% vs. 2.9%, P <0.0001). The R0 resection rate was 85.7% in the RNPLS group versus 82.9% in the NPLS group. The RNPLS group achieved a significantly higher ORR compared to the NPLS group (68.6% vs. 25.7%, P = 0.001), while DCRs were comparable between the two groups (94.3% vs. 77.1%, P = 0.055). Treatment-related adverse events (TRAEs) were confined to Grade 1-2 severity, with no Grade 3-4 events reported in either group. The RNPLS group showed a TRAE incidence of 80.0%, versus 88.6% in the NPLS group ( P = 0.324). Neither group exhibited surgical complications during the study period. CONCLUSION:Ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 significantly enhances the pCR rate and ORR in neoadjuvant therapy of locally advanced GC patients, while maintaining an acceptable safety profile.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that, for the different cell invasion and migration assay experiments shown in Fig. 5 on p. 238, as many as four pairs of overlapping data panels were identified, such that these data panels had all apparently been derived from the same original source(s); in addition, a further pair of overlapping data panels was identified comparing between Fig. 5 and the cell migration and invasion assay experiments shown in Fig. 7. Owing to the large number of duplications of data that have been identified in this paper, the Editor of International Journal of Oncology has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 47: 231‑243, 2015; DOI: 10.3892/ijo.2015.2981].

Background RNA modifications represent a novel category of biological molecule alterations, characterized by three primary classes of proteins: writers, erasers, and readers. Numerous studies indicate that the dysregulation of these RNA modifications is linked to cancer development and may offer new therapeutic avenues for treatment. In our research, we focused on eight specific genes associated with RNA modifications (RMRGs) to comprehensively analyze their distinct functions in gastric cancer (GC). Furthermore, we aimed to elucidate the roles of RMRGs concerning clinicopathological characteristics, tumor microenvironment, and patient prognosis. Methods In this study, we examined the expression and mutations of RMRGs in gastric cancer (GC) using data from TCGA-STAD (The Cancer Genome Atlas; Stomach adenocarcinoma) and the gene expression omnibus (GSE66229). We identified two subtypes of RMRGs and three gene clusters through consensus clustering analysis, assessing their differences in prognosis and immune cell infiltration patterns. Subsequently, we developed an RMRGs score to evaluate GC prognosis and highlight general immune features within the tumor microenvironment (TME). Lastly, we focused on MAMDC2 to validate its expression in GC and explore the effects of a MAMDC2 inhibitor on GC tumor cells. Results We discovered 94 differentially expressed RMRGs common to both the TCGA-STAD and GEO datasets. Notable differences in prognosis and immune cell infiltration were observed between the two RMRGs subtypes and three gene clusters. The RMRGs score emerged as an independent prognostic factor related to the tumor microenvironment (TME) characteristics in gastric cancer (GC). Reducing MAMDC2 levels enhanced cell migration and invasion while decreasing proliferation in vitro. Conclusions In conclusion, this study comprehensively analyzed the role of RMRGs on GC. Our study firstly proposed RMRGs score and demonstrated its potential to be biomarkers for prognosis and immune characteristics. Consequently, RMRGs score is of great clinical significance and can be utilized to develop individualized.

The incidence of IgG4-related autoimmune pancreatitis (IgG4-AIP) is high in Asia and other countries, and unnecessary treatment is often undertaken due to both missed diagnosis and misdiagnosis in clinical practice. Although IgG4-AIP has attracted increasing attention, the details of IgG4-AIP pathogenesis and systemic immune response, including its relationship to tumor pathogenesis, are still unclear. In recent years, research on serum immunological detection, pathological features, clinical manifestations, diagnosis and treatment measures for IgG4-AIP has gradually increased. It is of great importance to summarize and discuss the latest progress regarding IgG4-AIP disease.

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) "reader" protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1.

Objective:This study aimed to compare the feasibility and short-term clinical efficacy of triple-port laparoscopic distal gastrectomy (TPLDG) with five-port laparoscopic distal gastrectomy (FPLDG).Methods:From April 2020 to December 2021, this retrospective study included all consecutive patients (n = 21) who underwent TPLDG + D2 lymph node dissection, and randomly screened patients who underwent FPLDG + D2 lymph node dissection during this period (n = 30).Results:There were no significant differences in intraoperative (P > 0.05) and postoperative complication rate (P = 0.635) between the two groups. The changes in the first ambulation, flatus, water intake after surgery and postoperative hospitalization were also similar between the two groups (P > 0.05). However, time to abdominal drainage tube removal (1.62 ± 0.15 days vs. 2.00 ± 0.12 days, P = 0.046), NRS pain score on the first postoperative day (1.91 ± 0.15 days vs. 2.47 ± 0.12 days, P = 0.004) and hemameba level on the third postoperative day (7.89 ± 0.51 days vs. 10.52 ± 0.58 days, P = 0.002) were significantly lower in the TPLDG group compared to the FPLDG group.Conclusion:TPLDG is a safer, feasible, and short-term alternative to conventional LDG for distal gastric cancer.

Abstract Background In gastric cancer, there is a controversial finding regarding the high recurrence rate after neoadjuvant therapy. The use of ctDNA detection for minimal residual disease (MRD) with plasma genotyping has shown higher sensitivity and specificity compared to imaging and serum markers for predicting recurrence. Therefore, we aim to investigate the perioperative dynamic changes in ctDNA in surgical II-III GS patients and assess the efficacy of neoadjuvant chemotherapy. Methods In detail, we will collect blood samples from each patient before neoadjuvant chemotherapy (NAC), after NAC, and one month after surgery. We will also collect tumor tissue before and after NAC. Gene mutations will be detected using a 733-gene NGS panel, and DNA concentrations will be measured. To evaluate the effectiveness of the treatment, we will use RECIST Version 1.1 (RECIST 1.1). Discussion This study aims to assess the correlation between perioperative changes in ctDNA levels and the response to chemotherapy in patients with gastric cancer. It will provide evidence that perioperative ctDNA detection may predict early recurrence, highlighting the potential clinical utility of ctDNA in guiding therapeutic decision-making. Compared to tumor tissue biopsy, ctDNA can non-invasively detect more comprehensive genomic information from a limited amount of plasma. Trial registration: Registered prospectively in the Chinese Clinical Trials Registry with registration number ChiCTR2200060842 on June 12st, 2022.

Introduction Fifteen to 25% of patients with colorectal cancer have combined liver metastases at the time of diagnosis, whereas an additional 15 to 25% will develop liver metastases after curative resection of primary colorectal cancer, with the vast majority (80–90%) of liver metastases unresponsive to curative resection at first. Colorectal cancer liver metastasis is also the leading cause of death in patients with colorectal cancer. In recent years, several studies have demonstrated that intestinal flora, especially Fusobacterium nucleatum , plays a crucial role in the development of colorectal cancer liver metastasis, so we hypothesized that long-term metronidazole use could effectively reduce the incidence of postoperative liver metastasis in colorectal cancer patients. Methods/design This study is a prospective, single-centre, randomized, double-blind controlled study in which 300 patients will be randomly assigned to the test group or the control group in a 1:1 allocation ratio. The aim of this trial is to demonstrate that long-term oral antibiotics can effectively reduce the incidence of postoperative liver metastasis in patients with colorectal cancer. Ethics and dissemination Ethics approval was obtained from the Ethics Committee at the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20210229). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Trial registration Chinese Clinical Trial Registry ChiCTR2100046201. Registered on July 05, 2021.

At present, preoperative chemotherapy is the standard of care for the neoadjuvant treatment of potentially resectable gastric cancer (GC). However, because the efficacy and prognosis are not ideal, curative effects for this population are unsatisfactory. With the development of immune checkpoint inhibitors, the results of a few encouraging early trials of immunotherapeutic agents as neoadjuvant therapies for resectable GC have been reported. However, markers of the efficacy of immune checkpoint inhibitors remain unclear. This prospective single-center, single-arm observational study was designed to evaluate the efficacy of sintilimab plus the fluorouracil, leucovorin, oxaliplatin and docetaxel regimen as a neoadjuvant treatment for localized GC. More importantly, this work assesses multiple dimensions and include ctDNA, the immune microenvironment and intestinal microbiome to explore correlations between biomarkers and neoadjuvant therapeutic efficacy.Clinical trial registration: ChiCTR2200061629 (www.chictr.org.cn/index.aspx)

Objective To study the value of Onodera’s prognostic nutrition index (PNI) in patients with gastric neuroendocrine cancer (G-NEC). Methods The clinical data on 148 cases of G-NEC presented between March 2010 and April 2022 were retrospectively analyzed. The relationship between the clinical characteristics of the patients and PNI was analyzed. Optimal PNI cutoff values for G-NEC prognosis prediction were calculated using the X-tile software. The survival curves were created using the Kaplan–Meier method. A Cox proportional hazards model was also established to identify independent prognostic factors that impact the prognosis of patients with G-NEC. Results The median overall survival (OS) rate was 30 months (range 6–127 months), and the OS rates at 1, 3 and 5 years were 89.2, 71.6 and 68.2%, respectively. The mean PNI of the 148 patients before the operation was 49.5 ± 8.0. The mean PNI of patients with anemia (p < 0.001) and abnormal carcinoembryonic antigen (p = 0.039) was significantly lower than that of patients without such comorbidities. The mean PNI of patients with Stage III tumors (p < 0.001) and postoperative complications was significantly lower (p = 0.005). PNI optimal cutoff values were 50 (p < 0.001). Based on the cut-off value of the PNI, these patients were divided into a PNI-high group (PNI ≥ 50.0, n = 77) and a PNI-low group (PNI < 50.0, n = 71). The PNI-high group had a significantly better 5-years OS rate compared with the PNI-low group (76.6% vs. 59.2%, χ2 = 14.7, p < 0. 001). Multivariate analysis demonstrated that PNI and pathological stage were independent prognostic factors for patients with G-NEC. In the subgroup analysis, OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III of the disease. Conclusion The PNI is a simple and useful marker for predicting long-term outcomes in G-NEC patients regardless of tumor stage. Based on our results, we suggest that PNI should be included in routine assessments of patients with G-NEC.

胃癌是全球最常见和最致命的癌症之一.虽然手术、放化疗和免疫治疗的组合提高了胃癌患者的生存率,但大多数患者仍然会出现复发和转移,从而导致预后不良.目前胃癌血液生物标志物的敏感性和特异性不足以确定诊断和预后,因此应进一步探索和验证液体活检,以便在胃癌患者的临床中应用.区别于组织活检,液体活检分析对象包括血液、脑脊液、唾液、尿液等,具有迅速、便捷、无创等优势,本文重点介绍循环肿瘤细胞、循环肿瘤DNA和外泌体的临床应用,并探讨了其在胃癌患者临床需求方面的应用前景.

Nuclear-enriched RNA-binding proteins (RBPs) are mainly involved in transcriptional regulation, which is a critical checkpoint to tune gene diversity and expression levels. We analyzed nuclear RBPs in human HCC tissues and matched normal control tissues. Based on the gene expression levels, PTBP3 was identified as top-ranked in the nuclei of HCC cells. HCC cell lines then were transfected with siRNAs or lentiviral vectors. PTBP3 promoted HCC cell proliferation and metastasis both in vitro and in vivo. RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and qRT-PCR assays verified that PTBP3 protein recruited abundant lnc-NEAT1 splicing variants (NEAT1_1 and NEAT1_2) and pre-miR-612 (precursor of miR-612) in the nucleus. NEAT1_1, NEAT1_2 and miR-612 expression levels were determined by PTBP3. Correlational analyses revealed that PTBP3 was positively correlated with NEAT1, but it was inversely correlated with miR-612 in HCC. The P53/CCND1 and AKT2/EMT pathways were determined by NEAT1 and miR-612 respectively in HCC. The PTBP3high and NEAT1high/miR-612low patients had a shorter overall survival. Therefore, nuclear-enriched RBP, PTBP3, promotes HCC cell malignant growth and metastasis by regulating the balance of splicing variants (NEAT1_1, NEAT1_2 and miR-612) in HCC.

Colorectal cancer (CRC) is one of the common malignant tumors of digestive tract. The morbidity and mortality of CRC are on the rise in China, which poses a great threat to the health of Chinese people. Ferroptosis is a novel cell death pattern that accumulates in iron-dependent lipid peroxides and is widely present in various types of tumor cells. Ferroptosis-related genes have shown great potential in predicting the prognosis of CRC patients. What is more, the resistance of CRC to first-line anticancer drugs is gradually increasing, and accumulating evidence shows that ferroptosis is closely related to the resistance of first-line cancer drugs. This article will review the research progress of ferroptosis in the field of CRC in recent years, so as to provide a new perspective for improving cancer drug resistance of CRC and related drug development.

This study aimed to compare the effects of continuous hand-sewn esophagojejunostomy with barbed suture and mechanical anastomosis in total laparoscopic gastrectomy for esophagogastric junction cancer. The clinical data of 60 patients who underwent total laparoscopic total gastrectomy from January 2020 to October 2021 were collected retrospectively. Baseline data and short-term surgical results of patients in the hand-sewn anastomosis (n = 30) and mechanical anastomosis (n = 30) groups were analyzed. No significant differences were detected in the baseline data between groups. Meanwhile, the hand-sewn group had a shorter anastomosis time (21.2 ± 4.9 min vs. 27.9 ± 6.9 min, p < 0.001) and a decreased operation cost (CNY 70608.3 ± 8106.7 vs. CNY 76485.6 ± 3149.9, p = 0.001). The tumor margin distance in the hand-sewn group was longer than in the mechanical group (2.7 ± 0.4 cm vs. 2.2 ± 0.75 cm, p = 0.002). In esophagojejunostomy anastomosis, the distance between the jejunal opening and jejunal stump in the hand-sewn group was significantly shorter than that in the mechanical group (2.2 ± 0.54 cm vs. 5.7 ± 0.6 cm, p < 0.001). No significant difference was detected in the incidence of postoperative anastomotic complications. The continuous hand-sewn anastomosis with barbed suture in total laparoscopic gastrectomy for esophagogastric junction cancer is practical, safe, and cost-effective. It is also an effective supplementary technique for mechanical anastomosis.

非酒精性脂肪性肝病(NAFLD)对人类健康造成了巨大威胁.大约25％的NAFLD患者发展为非酒精性脂肪性肝炎(NASH),对我国造成了十分严重的卫生经济负担.研究人员致力于研究NASH发病的潜在分子机制,提出新的治疗方法.近期研究表明,炎症小体和gasdenmin-D(GSDMD)介导的炎症性程序性细胞死亡与NASH的发生发展有关.本文就NASH发病机制中细胞焦亡及其相关分子的研究进展作一综述.

Background: The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. Methods: In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. Results: Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's kappa, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). Conclusion: Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.

A 49-year-old man was referred to the hospital with the complaints of haematochezia and weight loss. Colonoscopy and pathological needle biopsy suggested moderately to highly differentiated adenocarcinoma. The patient underwent abdominal CT examination, which demonstrated two augmented and irregular masses in the liver. However, the glucose metabolism of 18F-FDG in these two lesions was completely different. Considering the different glucose metabolism, a needle biopsy of the liver mass was performed, and the diagnosis was rectal cancer with liver metastasis and primary hepatocellular carcinoma.

本研究比较全腹腔镜根治性全胃切除术中倒刺线连续手工缝合法与Overlap吻合。结果表明：手工缝合组吻合时间更短，肿瘤切缘距离更长，空肠开口部位距离空肠残端距离更短。手工倒刺线缝合法食管空肠吻合术是安全可行的。

Abstract Introduction The optimal preoperative preparation for elective colorectal cancer surgery has been debated in academic circles for decades. Previously, several expert teams have conducted studies on whether preoperative mechanical bowel preparation and oral antibiotics can effectively reduce the incidence of postoperative complications, such as surgical site infections and anastomotic leakage. Most of the results of these studies have suggested that preoperative mechanical bowel preparation for elective colon surgery has no significant effect on the occurrence of surgical site infections and anastomotic leakage. Methods/design This study will examine whether oral antibiotic bowel preparation (OABP) influences the incidence of anastomotic leakage after surgery in a prospective, multicentre, randomized controlled trial that will enrol 1500 patients who require colon surgery. The primary endpoint, incidence of anastomotic leakage, is based on 2.3% in the OABP ± mechanical bowel preparation (MBP) group in the study by Morris et al. Patients will be randomized (1:1) into two groups: the test group will be given antibiotics (both neomycin 1 g and metronidazole 0.9 g) the day before surgery, and the control group will not receive any special intestinal preparation before surgery, including oral antibiotics or mechanical intestinal preparation. All study-related clinical data, such as general patient information, past medical history, laboratory examination, imaging results, and surgery details, will be recorded before surgery and during the time of hospitalization. The occurrence of postoperative fistulas, including anastomotic leakage, will be recorded as the main severe postoperative adverse event and will represent the primary endpoint. Ethics and dissemination Ethics approval was obtained from the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200173). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals. Protocol was revised on November 22, 2021, version 4.0. Trial registration ChiCTR2000035550 . Registered on 13 Aug 2020.