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5-Fluorouracil (5-FU) is currently the main drug used in chemotherapy for gastric cancer (GC). The main clinical problems of 5-FU therapy are insensitivity and acquired resistance to 5-FU. The mechanism of GC cell resistance to 5-FU is currently unknown. This study employed next-generation sequencing (NGS) to analyze the differentially expressed genes (DEGs) in chemotherapy-sensitive and non-sensitive GC tissues. In addition, a bioinformatics analysis was conducted using the GC dataset of GEO, and further validated and explored through experiments. Thyroid adenoma-associated gene (THADA) was highly expressed in GC tissues from chemotherapy-sensitive patients and was an independent prognostic factor in GC patients receiving postoperative 5-FU adjuvant chemotherapy. Notably, heightened THADA expression in GC cells was associated with the down-regulation of autophagy-related proteins (LC-3, ATG13, ULK1, and TFEB). Furthermore, the PI3K/AKT/mTOR signaling pathway and mTORC1 signaling pathway were remarkably increased in patients with elevated THADA expression. THADA expression was associated with mTOR, the core protein of the mTOR signaling pathway, and related proteins involved in regulating the mTORC1 signaling pathway (mLST8, RHEB, and TSC2). THADA exhibited inhibitory effects on autophagy and augmented the sensitivity of GC cells to 5-FU through the PI3K/AKT/mTOR signaling pathway. The findings suggest that THADA may be involved in the regulatory mechanism of GC cell sensitivity to 5-FU. Consequently, the detection of THADA in tumor tissues may bring clinical benefits, specifically for 5-FU-related chemotherapy administered to GC patients with elevated THADA expression.

Non-occlusive mesenteric ischemia (NOMI) is a type of acute mesenteric ischemia (AMI) with a high mortality rate mainly because of a delayed or misdiagnosis. Intra-abdominal sepsis is one of the risk factors for developing NOMI, and its presence makes early diagnosis much more difficult. An increase in routine abdominal surgeries carries a corresponding risk of abdominal infection, which is a complication that should not be overlooked. It is critical that physicians are aware of the possibility for intestinal necrosis in abdominal sepsis patients due to the poor survival rate of NOMI. This review aims to summarize advances in the diagnosis of NOMI, and focuses on the diagnostic challenges of mesenteric ischemia in patients with intra-abdominal sepsis.

Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating IL-17 and its contribution to tumor progression in human gastric cancer remain poorly understood. In this study, we enrolled 112 gastric cancer patients, immunofluorescence was used to evaluate the colocalization of CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17. Immunohistochemistry was used to evaluate the distribution of microvessel density (CD34), CD66b(+), CD68(+), and FoxP3(+) cells in different microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis and a Cox regression model. The results showed that mast cells, but not T cells or macrophages, were the predominant cell type producing IL-17 in gastric cancer. Significant positive correlations were detected between densities of mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells (Tregs). Furthermore, we found that the majority of vascular endothelial cells expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that increasing intratumor infiltrated mast cells and IL-17(+) cells, as well as MCT(+) IL-17(+) cells, were significantly associated with worse overall survival. These findings indicated that mast cells were the major source of IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted tumor progression by enhancing angiogenesis in the tumor microenvironment through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic factor in gastric cancer, indicating that immunotherapy targeting mast cells might be an effective strategy to control intratumor IL-17 infiltration, and consequently reverse immunosuppression in the tumor microenvironment, facilitating cancer immunotherapy.

The use of composite laminates is characterized by problems such as poor inter-layer bonding and susceptibility of material properties to fatigue cracking, which seriously threaten structural safety. Research on fatigue damage characteristics and fatigue life prediction of fiber-reinforced composites can help to solve such problems. Carbon fiber-reinforced epoxy resin matrix composite laminates are taken as the object of this study. By analyzing the fatigue failure process and the fatigue failure micromorphology of the specimen, the primary damage forms and fatigue damage characteristics of its fatigue failure were obtained. The fatigue failure process of fiber-reinforced composites was simulated using finite element analysis software ABAQUS and its UMAT subroutine function. The tensile–tensile fatigue damage characteristics and failure mechanism of fiber-reinforced composites were studied, and the fatigue life of the composites was predicted. The feasibility of this life prediction method was verified by comparing it with experimentally obtained damage processes and fatigue lives. This intuitive and reliable life prediction method has good research potential for predicting the fatigue limit of fiber-reinforced composites.

Background and Purpose Levornidazole is an ornidazole derivative effective against anaerobic pathogens. Levornidazole disodium phosphate, the disodium phosphate salt of levornidazole, exhibits higher water solubility compared to levornidazole. This study aimed to evaluate the efficacy and safety of levornidazole disodium phosphate in patients with intra-abdominal infections (IAIs) caused by anaerobic pathogens. Methods This non-inferiority trial enrolled patients with IAIs in China, randomized 1:1 to either 1 g levornidazole disodium phosphate intravenously once daily (levornidazole group) or 0.5 g ornidazole and sodium chloride intravenously twice daily (control group) for 4–7 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit. The non-inferiority margin was −8%. Secondary endpoints included the bacterial eradication rate, overall success rate at both TOC and the end of therapy (EOT) visits, and clinical cure rate at the EOT visit. Results The full analysis set included 339 patients in the levornidazole group and 338 patients in the control group. At TOC, the clinical cure rates were 92.33% in the levornidazole group and 93.05% in the control group, with a between-group difference of −0.72% (95% CI: −4.85, 3.35). Clinical cure rates at EOT, bacteriological eradication rates, and overall success rates at EOT and TOC were similar in the two groups. The incidence of adverse drug reactions was 9.86% (34/345) in the levornidazole group and 12.17% (42/345) in the control group. Conclusions Once-daily levornidazole disodium phosphate was non-inferior to twice-daily ornidazole and sodium chloride for treating IAI, offering a more convenient, better-tolerated option due to its lower dosing frequency.

Colorectal cancer (CRC) is one of the most prevalent cancers among males and females worldwide. Despite progress in diagnostic and therapeutic strategies for CRC patients, the prognosis for patients with advanced CRC remains poor. MicroRNAs (miRNAs/miRs) are a class of highly conserved short, endogenously expressed and single‑stranded non‑coding RNAs. In recent years, increasing studies have demonstrated that dysregulation of miRNAs is closely associated with CRC carcinogenesis and progression. The aim of the present study was to explore the expression, roles and underlying molecular mechanism of miR‑130a in CRC. The results indicated that miR‑130a was significantly upregulated in CRC, and that miR‑130a expression levels were correlated with TNM stage and lymph node metastasis of CRC. Inhibition of miR‑130a markedly suppressed colorectal cancer cell proliferation, migration and invasion. Furthermore, forkhead box F2 (FOXF2) was identified as a direct downstream target gene of miR‑130a in colorectal cancer. Downregulation of FOXF2 could partially reverse the functions induced by miR‑130a under‑expression in CRC cells. These findings suggested that miR‑130a can regulate FOXF2 and function as an oncogene in CRC. Therefore, miR‑130a may serve as a useful therapeutic agent for miRNA‑based CRC targeted therapy.

Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. Lin28 has been shown to contribute to tumor relapse after chemotherapy; however, the relationship between Lin28 and chemoresistance remained unknown. In this study, we investigated the association of Lin28 with paclitaxel resistance and identified the underlying mechanisms of action of Lin28 in human breast cancer cell lines and tumor tissues. We found that the expression level of Lin28 was closely associated with the resistance to paclitaxel treatment. The T47D cancer cell line, which highly expresses Lin28, is more resistant to paclitaxel than the MCF7, Bcap-37 or SK-BR-3 cancer cell lines, which had low-level expression of Lin28. Knocking down of Lin28 in Lin28 high expression T47D cells increased the sensitivity to paclitaxel treatment, while stable expression of Lin28 in breast cancer cells effectively attenuated the sensitivity to paclitaxel treatment, resulting in a significant increase of IC50 values of paclitaxel. Transfection with Lin28 also significantly inhibited paclitaxel-induced apoptosis. We also found that Lin28 expression was dramatically increased in tumor tissues after neoadjuvant chemotherapy or in local relapse or metastatic breast cancer tissues. Moreover, further studies showed that p21, Rb and Let-7 miRNA were the molecular targets of Lin28. Overexpression of Lin28 in breast cancer cells considerably induced p21 and Rb expression and inhibited Let-7 miRNA levels. Our results indicate that Lin28 expression might be one mechanism underlying paclitaxel resistance in breast cancer, and Lin28 could be a potential target for overcoming paclitaxel resistance in breast cancer.

Background Gastric cancer (GC) patients often have nutritional risks or malnutrition, and neoadjuvant chemotherapy (NAC) tends to exacerbate malnutrition. Body composition parameters are associated with the prognosis of GC patients. Little is known about body composition changes during NAC and its role in clinical outcomes. Methods This was a secondary analysis of a Phase 3, open‐label, multicentre, randomized clinical trial (RCT) (NCT01364376), assessing the usefulness, safety and efficacy of S‐1 plus oxaliplatin (SOX) vs. fluorouracil, leucovorin and oxaliplatin (FOLFOX) as a perioperative chemotherapy regimen for patients with locally advanced GC. Pre‐NAC and post‐NAC computer tomography (CT) were collected to evaluate the prognostic role of skeletal muscle, adipose tissue and their dynamic change. Overall survival (OS) and progression‐free survival (PFS) rates were calculated using the Kaplan–Meier method. Results A total of 583 patients from 12 Chinese hospitals were enrolled. After exclusion, 423 patients who proceeded to surgery were used for further analysis. The median age was 60 (IQR: 54, 66) years, and 133 patients (31.4%) were female. Prior to NAC, 132 (31.2%) patients were diagnosed with sarcopenia. There was no significant difference in overall survival between sarcopenia and non‐sarcopenia patients (p = 0.363). During NAC, most patients suffered skeletal muscle (SM) loss (n = 268, 63.4%), subcutaneous adipose tissue (SAT) loss (n = 236, 55.8%) and visceral adipose tissue (VAT) loss (n = 254, 60.0%). Patients with SAT loss > 12.5% had significantly worse PFS (p = 0.005) and OS (p = 0.003) than those without. Patients with VAT loss > 15% had significantly worse PFS (p = 0.003) and OS (p = 0.004) than the stable or gain group. Patients with SMI loss > 4.7% had significantly worse PFS (p = 0.043) and showed a tendency of reduced OS (p = 0.181) than those without. In patients without sarcopenia, the incidence of grade 3/4 neutropenia in the FOLFOX group was higher than that of the SOX group (p = 0.019). In patients with myosteatosis, the incidence of Grade 3/4 thrombocytopenia in the SOX group was higher than that of the FOLFOX group (p < 0.001). Conclusion In this RCT study, patients with GC experience significant losses of muscle and adipose tissue during NAC. A high level of adipose tissue or muscle loss during NAC is prognostic of reduced survival in patients with locally advanced GC. Assessing and monitoring body composition can predict prognosis and effectively guide individual nutrition intervention and the prevention of complications.

Background The safety of laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer remains lack of clinical evidence. The Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group recently launched a multicenter randomized clinical trial (CLASS02–01) to compare the safety of LTG for clinical stage I gastric cancer with the conventional open total gastrectomy (OTG). Methods This CLASS02–01 trial is a prospective, multicenter, randomized, controlled, open, and non-inferiority trial. Two hundred patients who met the inclusion criteria and did not accord with the exclusion criteria will be randomly divided into LTG group ( n  = 100) and OTG group (n = 100). The primary purpose of this study is to evaluate the early operative morbidity and mortality of LTG compared with OTG for clinical stage I gastric adenocarcinoma. The second purpose is to evaluate the recovery course and compare the postoperative hospital stay of the patients enrolled in this study. Discussion This CLASS02–01 trial is the first prospective randomized two-arm controlled study to determine the safety of LTG compared with OTG. Through this trial, we hope to show that experienced surgeons can safely perform LTG with lymphadenectomy for gastric cancer. Trial registration ClinicalTrials.gov ID: NCT03007550 . December 30, 2016.

Background: Immune checkpoint inhibitors have shown promising results in the treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Objectives: To evaluate the safety and efficacy of camrelizumab combined with S-1 plus oxaliplatin chemotherapy in the postoperative setting for pathological stage III (pStage III) G/GEJ adenocarcinoma. Design: This study was a prospective, multicenter, single-arm, phase II trial. Methods: Patients with pStage III G/GEJ adenocarcinoma were enrolled, receiving camrelizumab (200 mg), followed by oxaliplatin (130 mg/m2), both administered on day 1 of each 21-day cycle, and tegafur–gimeracil–oteracil potassium capsules (40–60 mg, twice daily) for 2 weeks, followed by a 7-day rest period. A total of eight treatment cycles were planned. The primary endpoints were the incidence of any-grade and grade 3 or 4 adverse events. The secondary endpoints were disease-free survival (DFS), overall survival (OS), and treatment completion rate. Results: Between September 2020 and March 2023, 52 patients were enrolled at three medical centers in Zhejiang Province, China. All 52 patients (100%) experienced treatment-related adverse events (TRAEs). Grade 3 or higher TRAEs were reported in 35 patients (67.3%). Events occurring in >10% of the patients included decreased neutrophil count, neutropenia, leukopenia, thrombocytopenia, and anemia. Eleven (21.2%) patients experienced TRAEs that led to the interruption or discontinuation of camrelizumab, including rash (1), hypothyroidism (1), hyperkalemia (1), interstitial pneumonia (2), cystitis or urethritis (2), and reactive cutaneous capillary endothelial proliferation (4). The actual 2-year DFS and OS rates were 82.4% and 86.3%, respectively, whereas the estimated 3-year DFS and OS rates were 69.1% and 71.3%, respectively. Conclusion: Camrelizumab combined with chemotherapy has a manageable and tolerable safety profile as an adjuvant treatment for pStage III G/GEJ adenocarcinoma. However, careful patient selection is necessary to identify patients most likely to benefit from combination therapy. Trial registration: ClinicalTrials.gov registry: NCT04515615; Date of registration: August 14, 2020; Weblink: https://clinicaltrials.gov/study/NCT04515615.