POU2F2-oriented network promotes human gastric cancer metastasis.

BACKGROUND AND AIMS: Aberrant upregulation of POU2F2 expression has been discovered in metastatic gastric cancer (GC). However, the mechanisms underlying the aberrant upregulation and the potential functions of POU2F2 remain uncertain. DESIGN: The role and mechanism of POU2F2 in GC metastasis were investigated in gastric epithelial cells, GC cell lines and an experimental metastasis animal model by gain of function and loss of function. Upstream and downstream targets of POU2F2 were selected by bioinformatics and identified by luciferase reporter assay, electrophoretic mobility shift assay and chromatin immunoprecipitation PCR. The influence of miR-218 on its putative target genes (POU2F2, ROBO1 and IKK-ß) and GC metastasis was further explored via in vitro and in vivo approaches. RESULTS: Increased POU2F2 expression was detected in metastatic GC cell lines and patient samples. POU2F2 was induced by the activation of nuclear factor (NF)-κB and, in turn, regulated ROBO1 transcription, thus functionally contributing to GC metastasis. Finally, miR-218 was found to suppress GC metastasis by simultaneously mediating multiple molecules in the POU2F2-oriented network. CONCLUSIONS: This study demonstrated that NF-κB and the SLIT2/ROBO1 interaction network with POU2F2 as the central part may exert critical effects on tumour metastasis. Blocking the activation of the POU2F2-oriented metastasis network using miR-218 precursors exemplified a promising approach that sheds light on new strategies for GC treatment.

MGr1-Ag/37LRP induces cell adhesion-mediated drug resistance through FAK/PI3K and MAPK pathway in gastric cancer.

It is well known that tumor microenvironment plays a vital role in drug resistance and cell adhesion-mediated drug resistance (CAM-DR), a form of de novo drug resistance. In our previous study, we reported that MGr1-Ag/37LRP ligation-induced adhesion participated in protecting gastric cancer cells from a number of apoptotic stimuli caused by chemotherapeutic drugs. Further study suggested that MGr1-Ag could prompt CAM-DR through interaction with laminin. However, the MGr1-Ag-initiated intracellular signal transduction pathway is still unknown. In this study, our experimental results showed that gastric cancer MDR cell lines mediated CAM-DR through upregulation of Bcl-2 by MGr1-Ag interaction with laminin. Further study found that, as a receptor of ECM components, MGr1-Ag/37LRP may activate the downstream signal pathway PI3K/AKT and MAPK/ERK through interaction with phosphorylated FAK. Moreover, the sensitivity to chemotherapeutic drugs could be significantly enhanced by inhibiting MGr1-Ag/37LRP expression through mAbs, siRNA, and antisense oligonucleotide. According to these results, we concluded that the FAK/PI3K and MAPK signal pathway plays an important role in MGr1-Ag-mediated CAM-DR in gastric cancer. MGr1-Ag/37LRP might be a potential effective reversal target to MDR in gastric cancer.

Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma.

We aimed to evaluate the influence of sirtuin1 (sirt1) on the ESCC chemotherapeutic sensitivity to cisplatin. We used ESCC cell ablation sirt1 for establishing a xenograft mouse tumor model. The tumor volume was then detected. sirt1 was over-expressed significantly in ESCC patients and cells. Moreover, sirt1 knockdown raised ESCC sensitivity to cisplatin. Besides, glycolysis was associated with ESCC cell chemotherapy resistance to cisplatin. Furthermore, sirt1 increased ESCC cells' cisplatin chemosensitivity through HK2. Sirt1 enhanced in vivo ESCC chemosensitivity to cisplatin. Overall, these findings suggested that sirt1 knockdown regulated the glycolysis pathway and raised the ESCC chemotherapeutic sensitivity.

Early enteral nutrition versus early supplemental parenteral nutrition in patients undergoing major abdominal surgery: a secondary analysis of 2 randomized clinical trials.

BACKGROUND: The effect of early isoenergetic feeding routes [early enteral nutrition (E-EN) or early supplemental parenteral nutrition (E-SPN)] on the outcome of patients undergoing major abdominal surgery is controversial. OBJECTIVES: The aim of this study was to investigate the impact of early isoenergetic EN compared with early isoenergetic SPN on nosocomial infections in patients undergoing major abdominal surgery. METHODS: This study is a secondary, post hoc analysis of data from 2 open-label randomized clinical trials. Participants were recruited from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and with Nutritional Risk Screening 2002 score ≥3. All eligible patients were categorized into 2 groups based on their achievement of the 100% energy target on postoperative day (POD) 3: the E-EN group (n = 199) and the E-SPN group (n = 115). The primary outcome was the incidence of nosocomial infections between POD 3 and hospital discharge. RESULTS: In total, 314 patients [mean (SD) age, 59.2 (11.4) y; 113 (36.0%) females] were included. Patients in the E-EN group showed no significant difference in nosocomial infections compared with those in the E-SPN group {17/199 [8.5%] compared with 10/115 [8.7%], risk difference, 0.2% [95% confidence interval (CI): -6.3, 6.6]}. The hematological nutritional status of the E-EN group showed a significant improvement at discharge compared with the E-SPN group (albumin: 38.0 ± 6.0 g/L compared with 35.5 ± 7.6 g/L; mean difference, -2.5 g/L; 95% CI: -4.0, -1.0 g/L; prealbumin: 200.0 ± 8.0 mg/L compared with 158.4 ± 38.1 mg/L; mean difference, -41.6 mg/L; 95% CI: -41.7, -36.1 mg/L). Other indicators were comparable between groups. CONCLUSION: E-EN compared with isoenergetic SPN may not be associated with a reduced rate of nosocomial infection in patients undergoing major abdominal surgery, but may be associated with improved hematological nutritional status. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT03115957 (https://clinicaltrials.gov/ct2/show/NCT03115957) and NCT03117348 (https://clinicaltrials.gov/ct2/show/NCT03117348).

Development and validation of serological dynamic risk score to predict outcome in gastric cancer with adjuvant chemotherapy: a multicentre, longitudinal, cohort study.

Background: Baseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests. Materials and methods: This was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters. Results: The Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction <0.0001). Compared with the low-low-low risk group, the low-low-high risk group of the long-term state chain (risk state at baseline, 6 months, 1 year) had the worse OS (HR, 6.91; 95%CI: 4.27, 11.19) and DFS (HR, 7.27; 95%CI: 4.55, 11.63). Conclusion: The dynamic risk score is an accurate and user-friendly serological risk assessment tool for predicting outcomes and assisting clinical decisions after gastrectomy.

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01).

Objective: Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer. Methods: and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR). Ethics: Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1). Trial registration: This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

Surgical resection should be taken into consideration for the treatment of small gastric gastrointestinal stromal tumors.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) recommends conservative follow-up for gastric gastrointestinal stromal tumors (GISTs) less than 2 cm. The aim of the present study was to investigate the clinical and pathological features of small gastric GISTs, re-evaluate the risk potential, and discuss the treatment strategy of small gastric GISTs. METHODS: In this retrospective study, 63 cases of small gastric GISTs (less than 2 cm) were resected surgically from May 2010 to March 2013 in our department. Clinicopathological factors were collected and the malignant potential of small gastric GISTs was analyzed. RESULTS: The mitotic index of 14 out of 63 cases (22.22%) exceeded 5. The malignant potential of small gastric GISTs was related to tumor location (P = 0.0218). The mitotic index of 4 out of 8 GISTs (50%) located in gastric cardia exceeded 5, 8 out 28 GISTs (28.57%) located in the gastric fundus exceeded 5, and only 2 out of 27 GISTs (7.41%) located in the gastric body exceeded 5. We also discovered a good consistency between mitotic index and Ki-67 expression of small gastric GISTs. CONCLUSIONS: Gastric GISTs less than 2 cm also have malignant potential. Thus, we recommended surgical resection of all small gastric GISTs once diagnosed.

Robust and efficient abdominal CT segmentation using shape constrained multi-scale attention network.

PURPOSE: Although many deep learning-based abdominal multi-organ segmentation networks have been proposed, the various intensity distributions and organ shapes of the CT images from multi-center, multi-phase with various diseases introduce new challenges for robust abdominal CT segmentation. To achieve robust and efficient abdominal multi-organ segmentation, a new two-stage method is presented in this study. METHODS: A binary segmentation network is used for coarse localization, followed by a multi-scale attention network for the fine segmentation of liver, kidney, spleen, and pancreas. To constrain the organ shapes produced by the fine segmentation network, an additional network is pre-trained to learn the shape features of the organs with serious diseases and then employed to constrain the training of the fine segmentation network. RESULTS: The performance of the presented segmentation method was extensively evaluated on the multi-center data set from the Fast and Low GPU Memory Abdominal oRgan sEgmentation (FLARE) challenge, which was held in conjunction with International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) 2021. Dice Similarity Coefficient (DSC) and Normalized Surface Dice (NSD) were calculated to quantitatively evaluate the segmentation accuracy and efficiency. An average DSC and NSD of 83.7% and 64.4% were achieved, and our method finally won the second place among more than 90 participating teams. CONCLUSIONS: The evaluation results on the public challenge demonstrate that our method shows promising performance in robustness and efficiency, which may promote the clinical application of the automatic abdominal multi-organ segmentation.

Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials.

BACKGROUND: The effect of early achievement of energy targets (EAETs) using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of EAETs on the incidence of nosocomial infections in patients undergoing major abdominal surgery. METHODS: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the EAET (521 EAET and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. RESULTS: Overall, 635 patients [mean (SD) age, 59.5 (11.3) years] were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 vs. 15.1±4.8 kcal/kg/d; P <0.001). The EAET group had significantly fewer nosocomial infections than the NAET group [46/521(8.8%) vs. 21/114(18.4%); risk difference, 9.6%; 95% CI, 2.1-17.1%; P =0.004]. A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups [121/521(23.2%) vs. 38/114(33.3%); risk difference, 10.1%; 95% CI, 0.7-19.5%; P =0.024]. The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group ( P <0.001), and other indicators were comparable between groups. CONCLUSION: EAETs was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).

M1 macrophage predicted efficacy of neoadjuvant camrelizumab combined with chemotherapy vs chemotherapy alone for locally advanced ESCC: A pilot study.

Introduction: The efficacy and safety of immunotherapy have been widely recognized in gastrointestinal-related cancers. However, the efficacy of neoadjuvant camrelizumab for locally advanced esophageal squamous cell carcinoma (ESCC) has not been firmly established. This study compared the efficacy of camrelizumab in combination with neoadjuvant DCF (docetaxel, cisplatin and fluorouracil), with DCF alone for ESCC, and exploring biomarkers related to immune infiltration of the ESCC immunotherapy response. Methods: We enrolled and randomly assigned patients with stage II-IVa ESCC to two study treatments: camrelizumab combined with docetaxel, cisplatin and fluorouracil (DCF) regimen and DCF regimen alone. The tissue for multiplex immunofluorescence (mIF) was obtained before and after neoadjuvant therapy. The Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1) and Tumor Regression Grade (TRG) was used to evaluate efficacy. Results: A total of 30 patients were enrolled in the study. Following neoadjuvant camrelizumab, the objective response rate (ORR) and the disease control rate (DCR) were 46.7% (7/15) and 95.7% (14/15), respectively. No patients reported complete remission, while ORR and DCR in the chemotherapy group were 26.7% (4/15) and 86.7% (13/15), respectively. R0 resection after neoadjuvant treatment was achieved in 3 out of 15 patients in the combined group and in all patients (15/15) in the chemotherapy group. In the combined group, M1-type tumor-associated macrophages and CD56dim NK cells were more abundant in responders than in non-responders (p < 0.05). A higher M1/M2 ratio was observed in responders (p < 0.05). With respect to the NGS, among the copy number amplified genes, the 11q13 amplicon (CCND1/FGF19/FGF4/FGF3) showed the highest frequency (47%, 7/15). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy improved ORR in locally advanced ESCC. M1-type tumor-associated macrophages and CD56dim NK cells might be utilized to predict camrelizumab efficacy.

Association of CDX2 and mucin expression with chemotherapeutic benefits in patients with stage II/III gastric cancer.

BACKGROUND: Better predictors of patients with stage II/III gastric cancer (GC) most likely to benefit from adjuvant chemotherapy are urgently needed. This study aimed to assess the ability of CDX2 and mucin markers to predict prognosis and fluorouracil-based adjuvant chemotherapy benefits. METHODS: CDX2 and mucin protein expressions were examined by immunohistochemistry and compared with survival and adjuvant chemotherapy benefits in a prospective evaluation cohort of 782 stage II/III GC patients. Then, the main findings were validated in an independent validation cohort (n = 386) and an external mRNA sequencing dataset (ACRG cohort, n = 193). RESULTS: In the evaluation cohort, CDX2, CD10, MUC2, MUC5AC, and MUC6 expressions were observed in 59.7%, 26.7%, 27.6%, 55.1%, and 57.7% of patients, respectively. However, only the expression of CDX2 was found to be associated with adjuvant chemotherapy benefits. Most importantly, CDX2-negative patients had a poorer prognosis when treated with surgery only, while the prognosis of CDX2-negative and CDX2-positive patients was similar when receiving postoperative adjuvant chemotherapy. Further analysis revealed that patients with CDX2 negative tumors benefited from chemotherapy (5-year overall survival rates: 60.0% with chemotherapy vs. 23.2% with surgery-only, p < 0.001), whereas patients with CDX2 positive tumors did not (pinteraction = 0.004). Consistent results were obtained in the validation and ACRG cohorts. CONCLUSIONS: Negative expression of CDX2 is an independent risk factor for survival in stage II/III GC, but subsequent adjuvant chemotherapy is able to compensate for this unfavorable effect. Therefore, active chemotherapy is more urgent for patients with negative CDX2 expression than for patients with positive CDX2 expression.

From polyvinyl chloride waste to activated carbons: the role of occurring additives on porosity development and gas adsorption properties.

Conversion of waste plastic to carbon materials has been considered as a potential approach for plastic recycling. In this study, polyvinyl chloride (PVC) plastic, one of the most widely used polymers, was used as a single precursor to prepare porous carbons via chemical activation process. The results showed that KOH activation followed by acid washing was an effective strategy to recover all calcium- and up to 92% of titanium-based compounds, the main metal additives in PVC, in the form of soluble salt. Those metal additives in PVC acted as a type of hard template, which benefit the development of microporosity and carbon dioxide (CO2) adsorption. Textural characterization demonstrated that the prepared carbons possessed high surface area and pore volume of up to 2507 m2/g and 1.11 cm3/g, respectively. At 0 °C and 100 kPa, the PVC-derived carbon, PH_73, which has highest ultra-micropore volume among all samples, exhibited excellent CO2 adsorption capacity of 6.90 mmol/g and high CO2/N2 selectivity. Converting the non-degradable PVC into high-quality porous carbon materials could be considered as a potential strategy for plastic waste recycling.

Let food be thy medicine: the role of diet in colorectal cancer: a narrative review.

Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, and the incidence and mortality rates continue to increase annually. Many factors, including genetic, immune, and environmental factors, influence the occurrence and development of CRC. Along with the economic development, changes in lifestyle, especially dietary factors, have been shown to greatly affect the progression of CRC. Increasing evidence showed that dietary patterns influence the risk of CRC and affect CRC treatment. The present review describes the role of diet in the prevention and treatment of CRC with the hope that doctors attach importance to dietary patterns in educating patients with CRC or at risk of CRC and that diet may be regarded as an auxiliary treatment strategy to improve patients' outcomes. Methods: English language articles published from 2000 to December 2021 in PubMed and Embase were identified by searching titles for keywords including "diet", "colorectal cancer", "dietary pattern", and "dietary factor"; 101 articles were selected for review. Key Content and Findings: The present review describes the role of different dietary patterns and factors in the prevention and treatment of CRC. We found that dietary intervention is closely related to the occurrence, development, and prognosis of CRC. Adherence to the Mediterranean diet (MD), the Dietary Approaches to Stop Hypertension (DASH) diet, fasting, vegetarian diets and the ketogenic diet (KD) were found to reduce the risk of CRC, prolong patient survival, and delay disease progression. Moderate intake of dietary fiber (DF), omega-3 fatty acids, micronutrients (e.g., calcium, iron, and selenium), and vitamins have been shown to be beneficial in the prevention and treatment of CRC. Conversely, diets high in fat or sugar and those rich in red meat or processed meat promote CRC. Conclusions: People at high risk of CRC and those with CRC are recommended to eat a plant-based diet rich in fruits, vegetables, and whole grains with appropriate DF intake and to avoid high levels of processed meat, red meat, and highly refined grains.

Case report: Long response to PD-1 blockade after failure of trastuzumab plus chemotherapy in advanced Epstein-Barr virus-associated gastric cancer.

Background: Trastuzumab-containing chemotherapy is the first-line treatment for advanced gastric cancer (GC) with HER2 positive. Although PD-1 inhibitors significantly improved the outcome of GC patient's refractory to previous chemotherapy regimens, few studies explore the role of anti-PD-1 therapy overcomes resistance to trastuzumab plus chemotherapy in advanced Epstein-Barr Virus-associated gastric cancer (EBVaGC) with PD-L1 and HER2 positive. Case Presentation: We report a case of advanced EBVaGC in a 45-year-old man presenting with fatigue, dysphagia, and weight loss for several months. Initial endoscopy revealed a large tumor at the gastroesophageal junction. Computed tomography revealed GC accompanied by multiple lymph nodes and hepatic and pulmonary metastases. The immunohistochemistry indicated that HER-2 and PD-L1 were overexpressed, and tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. Trastuzumab plus DCS was started as first-line chemotherapy with a PFS of 4 months and shifted to trastuzumab plus FOLFIRI or gemcitabine as second-/third-line therapy. After five-cycle nivolumab monotherapy, the patient received partial response and was treated with total radical gastrectomy plus sequential radiotherapy. He continued the postoperative immunotherapy over 30 cycles with a PFS of 28 months. Due to a new abdominal lymph node metastasis confirmed by PET-CT, he received toripalimab as the next-line treatment and achieved complete remission as the best objective response. Summary: We presented an advanced HER2-positive EBVaGC patient with PD-L1 high expression, refractory to trastuzumab plus chemotherapy, and had a durable clinical benefit sequence with a single dose of the PD-1 inhibitor.

Effect of Early vs Late Supplemental Parenteral Nutrition in Patients Undergoing Abdominal Surgery: A Randomized Clinical Trial.

Importance: The effect of and optimal timing for initiating supplemental parenteral nutrition (SPN) remain unclear after major abdominal surgery for patients in whom energy targets cannot be met by enteral nutrition (EN) alone. Objective: To examine the effect of early supplemental parenteral nutrition (E-SPN) (day 3 after surgery) or late supplemental parenteral nutrition (L-SPN) (day 8 after surgery) on the incidence of nosocomial infections in patients undergoing major abdominal surgery who are at high nutritional risk and have poor tolerance to EN. Design, Setting, and Participants: A multicenter randomized clinical trial was conducted from April 1, 2017, to December 31, 2018, in the general surgery department of 11 tertiary hospitals in China. Participants were those undergoing major abdominal surgery with high nutritional risk and poor tolerance to EN (≤30% of energy targets from EN on postoperative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) and an expected postoperative hospital stay longer than 7 days. Data analysis was performed from February 1 to October 31, 2020. Interventions: Random allocation to E-SPN (starting on day 3 after surgery) or L-SPN (starting on day 8 after surgery). Main Outcomes and Measures: The primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge. Results: A total of 230 patients (mean [SD] age, 60.1 [11.2] years; 140 men [61.1%]; all patients were of Han race and Asian ethnicity) were randomized (115 to the E-SPN group and 115 to the L-SPN group). One patient in the L-SPN group withdrew informed consent before the intervention. The E-SPN group received more mean (SD) energy delivery between days 3 and 7 compared with the L-SPN group (26.5 [7.4] vs 15.1 [4.8] kcal/kg daily; P < .001). The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (10/115 [8.7%] vs 21/114 [18.4%]; risk difference, 9.7%; 95% CI, 0.9%-18.5%; P = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (31/115 [27.0%] vs 38/114 [33.3%]; risk difference, 6.4%; 95% CI, -5.5% to 18.2%; P = .32), total adverse events (75/115 [65.2%] vs 82/114 [71.9%]; risk difference, 6.7%; 95% CI, -5.3% to 18.7%; P = .32), and rates of other secondary outcomes. A significant difference was found in the mean (SD) number of therapeutic antibiotic days between the E-SPN group and the L-SPN group (6.0 [0.8] vs 7.0 [1.1] days; mean difference, 1.0 days; 95% CI, 0.2-1.9 days; P = .01). Conclusion and Relevance: In this randomized clinical trial, E-SPN was associated with reduced nosocomial infections in patients undergoing abdominal surgery and seems to be a favorable strategy for patients with high nutritional risk and poor tolerance to EN after major abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03115957.

Poor Pre-operative Nutritional Status Is a Risk Factor of Post-operative Infections in Patients With Gastrointestinal Cancer-A Multicenter Prospective Cohort Study.

Objective: This study aimed to assess the prognostic value of the Nutritional Risk Score 2002 (NRS2002) and patient-generated subjective global assessment (PG-SGA) for post-operative infections in patients with gastric cancer (GC) and colorectal cancer (CRC) who underwent curative surgery. Methods: This prospective study included 1,493 GC patients and 879 CRC patients who underwent curative surgery at 18 hospitals in China between April 2017 and March 2020. The NRS2002 and PG-SGA were performed on the day of admission. The relationship between the nutritional status of patients before surgery and post-surgical incidence of infection was analyzed using univariate and multiple logistic regression analyses. Results: According to NRS2002, the prevalence of nutritional risk was 51.1% in GC patients and 63.9% in CRC patients. According to the PG-SGA, 38.9% of GC patients and 54.2% of CRC patients had malnutrition. Approximately 4.4% of the GC patients and 9.9% of the CRC patients developed infectious complications after surgery. The univariate and multiple logistic regression analyses showed that the risk of infections was significantly higher in GC patients with a high nutritional risk score (NRS2002 ≥5) than in those with a low score (NRS2002 <3), and the PG-SGA score was identified as a predictor of post-operative infection complications of CRC. Conclusion: The pre-operative nutritional status of patients with GC or CRC has an impact on post-operative infection occurrence. NRS2002 ≥5 was a risk factor for post-operative infection in patients with GC, and the PG-SGA B/C was a predictor of infections in patients with CRC.

Automated Segmentation Method for Low Field 3D Stomach MRI Using Transferred Learning Image Enhancement Network.

Accurate segmentation of abdominal organs has always been a difficult problem, especially for organs with cavities. And MRI-guided radiotherapy is particularly attractive for abdominal targets compared with low CT contrast. But in the limit of radiotherapy environment, only low field MRI segmentation can be used for stomach location, tracking, and treatment planning. In clinical applications, the existing 3D segmentation network model is trained by the low field MRI, and the segmentation result cannot be used in radiotherapy plan since the bad segmentation performance. Another way is that historical high field intensity MR images are directly used for data expansion to network learning; there will be a domain shift problem. How to use different domain images to improve the segmentation accuracy of deep neural network? A 3D low field MRI stomach segmentation method based on transfer learning image enhancement is proposed in this paper. In this method, Cycle Generative Adversarial Network (CycleGAN) is used to construct and learn the mapping relationship between high and low field intensity MRI and to overcome domain shift. Then, the image generated by the high field intensity MRI through the CycleGAN network is with transferred information as the extended data. The low field MRI combines these extended datasets to form the training data for training the 3D Res-Unet segmentation network. Furthermore, the convolution layer, batch normalization layer, and Relu layer together were replaced with a residual module to relieve the gradient disappearance of the neural network. The experimental results show that the Dice coefficient is 2.5 percent better than the baseline method. The over segmentation and under segmentation are reduced by 0.7 and 5.5 percent, respectively. And the sensitivity is improved by 6.4 percent.

Polygalacin D suppresses esophageal squamous cell carcinoma growth and metastasis through regulating miR-142-5p/Nrf2 axis.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide with poor survival. High expression of nuclear factor erythroid 2-related factor 2 (Nrf2) is an antioxidant transcript factor that protects malignant cells from death. Polygalacin D (PGD), a bioactive compound isolated from Platycodongrandiflorum (Jacq.), has recently been reported to be an anti-tumor agent. This study aimed to investigate the anti-cancer effects of PGD and its underlying molecular mechanisms in human ESCC. Here, we confirmed that Nrf2 was over-expressed in clinical ESCC tissues and cell lines. PGD treatments markedly reduced Nrf2 expression in a dose- and time-dependent manner in ESCC cell lines. Importantly, we found that PGD significantly reduced proliferation, and induced G2/M cell cycle arrest and apoptosis in ESCC cells. Also, PGD dramatically triggered autophagy in ESCC cells, and autophagy inhibitor bafilomycinA1 (BafA1) greatly abrogated the inhibitory role of PGD in cell viability and apoptosis. In addition, PGD evidently provoked reactive oxygen species (ROS) accumulation in ESCC cells, and pre-treatment of ROS scavenger N-acetyl-l-cysteine (NAC) markedly abolished PGD-triggered cell death. PGD also dramatically repressed migration and invasion in ESCC cells. Mechanistic investigation revealed that Nrf2 gene was directly targeted by miR-142-5p. MiR-142-5p negatively regulated Nrf2 expression in ESCC cells. We notably found that PGD-inhibited proliferation, migration and invasion in ESCC were considerably rescued by miR-142-5p knockdown; however, ROS production, apoptosis and autophagy induced by PGD were almost eliminated when miR-142-5p was silenced. On the contrast, over-expressing miR-142-5p could remarkably promote the anti-ESCC effects of PGD. Experiments in vivo by the tumor xenograft model confirmed that miR-142-5p effectively improved the activity of PGD to repress tumor growth and lung metastasis. Both in vitro and in vivo studies showed that PGD had few side effects on normal cells and major organs. Collectively, our findings provided the first evidence that PGD could be an effective therapeutic strategy for ESCC treatment by regulating miR-142-5p/Nrf2 axis with few adverse effects.

Association of systemic inflammation and body mass index with survival in patients with resectable gastric or gastroesophageal junction adenocarcinomas.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods: A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results: Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069-1.430; and HR: 1.600, 95% CI: 1.350-1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054-1.434; and HR: 1.658, 95% CI: 1.389-1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853-3.225) and RFS (HR: 2.405, 95% CI: 1.802-3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions: Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Immediate vs. gradual advancement to goal of enteral nutrition after elective abdominal surgery: A multicenter non-inferiority randomized trial.

BACKGROUND & AIMS: The strategy of increasing the postoperative enteral nutrition dose to the target goal has not yet been clarified. This study aimed to determine whether an immediate goal-dose enteral nutrition (IGEN) strategy is non-inferior to a gradual goal-dose enteral nutrition (GGEN) strategy in reducing infections in patients undergoing abdominal surgery involving the organs of the digestive system. METHODS: This randomized controlled trial enrolled postoperative patients with nutritional risk screening 2002 scores ≥3 from 11 Chinese hospitals. Energy targets were calculated as 25 kcal/kg and 30 kcal/kg of ideal body weight for women and men, respectively. Patients were randomly assigned 1:1 to IGEN or GGEN group after enteral tolerance was confirmed (30% of the target on day 2). The IGEN group immediately started receiving 100% of the caloric requirements on day 3, while the GGEN group received 40% progressing to 80% of target on day 7. The primary endpoint was the infection rate until discharge, based on the intention-to-treat population. RESULTS: A total of 411 patients were enrolled and randomized to the IGEN and GGEN groups, and five patients did not receive the allocated intervention. A total of 406 patients were included in the primary analysis, with 199 and 207 in the IGEN and GGEN groups, respectively. Infection was observed in 17/199 (8.5%) in the IGEN group and 19/207 (9.2%) in the GGEN group, respectively (difference, -0.6%; [95% confidence interval (CI), -6.2%-4.9%]; P = 0.009 for non-inferiority test). There were significantly more gastrointestinal intolerance events with IGEN than with GGEN (58/199 [29.1%] vs. 32/207 [15.5%], P < 0.001). All other secondary endpoints were non-significant. CONCLUSIONS: Among postoperative patients at nutritional risk, IGEN was non-inferior to GGEN in regards to infectious complications. IGEN was associated with more gastrointestinal intolerance events. It showed that IGEN cannot be considered to be clinically directive. ClinicalTrials.gov (#NCT03117348).