Upregulation of MELK promotes chemoresistance and induces macrophage M2 polarization via CSF-1/JAK2/STAT3 pathway in gastric cancer.

BACKGROUND: Gastric cancer (GC) stands out as one of the most prevalent malignancies affecting the digestive system, characterized by a substantial incidence rate and mortality. Maternal embryonic leucine zipper kinase (MELK) has been implicated in the advancement of various cancer types and the modulation of the tumor microenvironment. This study aims to delve into the involvement of MELK in chemoresistance and the tumor microenvironment of GC. METHODS: The MELK expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry. Lentiviral transfection was employed to establish stable cell lines with either overexpressed or silenced MELK. The impact of MELK on the chemoresistance of GC cells and the polarization of macrophages was investigated through in vitro and in vivo functional assays. Additionally, the correlation between MELK and the cytokines colony-stimulating factor 1 (CSF-1), as well as stromal macrophages, was analysed. The prognostic significance of MELK, CSF-1, and CD206 expression levels in clinical samples was further investigated. RESULTS: MELK was found to be highly expressed in chemoresistant GC cells and tissues. Furthermore, both in vitro and in vivo assays indicated that MELK overexpression conferred chemoresistance in GC cells. Additionally, MELK overexpression was observed to induce M2 macrophage polarization via the CSF-1/JAK2/STAT3 pathway, thereby contributing to chemoresistance within the tumor microenvironment. The expression of MELK in GC tissues from neoadjuvant chemotherapy patients correlated positively with CSF-1 and CD206. Moreover, patients with higher expression levels of MELK, CSF-1, or CD206 exhibited significantly shorter OS and DFS rates. CONCLUSIONS: Our investigation underscores the critical role of MELK in promoting chemoresistance and inducing M2 macrophage polarization in GC. It proposes novel targets and methods for the treatment of GC, as well as prognostic factors for neoadjuvant chemotherapy.

Poor sleep quality and overweight/obesity in healthcare professionals: a cross-sectional study.

Objective: This study aimed to analyze the relationship between the sleep quality of healthcare professionals and the incidence of overweight and obesity, exploring the potential impact of sleep quality on the onset of overweight and obesity in order to provide a scientific basis for formulating effective health intervention measures. Methods: A convenience sampling method was used to conduct a survey on the sleep characteristics and obesity status among healthcare professionals at Peking Union Medical College Hospital and Tianjin Dongli District Traditional Chinese Medicine Hospital. The survey was conducted via online questionnaires, which included demographic data, the Pittsburgh Sleep Quality Index (PSQI), height, weight, and related sleep, exercise, and dietary habits. Univariate and multivariate logistic regression analyses were applied to study the relationship between sleep quality and overweight/obesity among healthcare professionals. Results: A total of 402 questionnaires were distributed, with a 100% retrieval rate, yielding 402 valid questionnaires. The average body mass index of the 402 participants was 23.22 ± 3.87 kg/m^2. Among them, 144 cases were overweight or obese, accounting for 35.8% (144/402) of the total. The prevalence of poor sleep quality among healthcare professionals was 27.4% (110/402), with an average PSQI score of 8.37 ± 3.624. The rate of poor sleep quality was significantly higher in the overweight and obese group compared to the normal weight group (36.1% vs. 22.5%, p = 0.003). The multivariate analysis indicated that gender, marital status, lower education level, sleep duration (odds ratio [OR] =1.411, 95% confidence interval [CI] 1.043-1.910, p = 0.026), and sleep disturbances (OR = 1.574, 95%CI 1.123-2.206, p = 0.008) were significant risk factors for overweight and obesity among healthcare professionals. Conclusion: Overweight or obese healthcare professionals had poorer sleep quality compared to those with a normal weight. Sleep duration and sleep disorders were identified as independent risk factors for overweight or obesity in healthcare professionals. Increasing sleep duration and improving sleep disorders may play a positive role in controlling overweight and obesity among healthcare professionals.

Two nomograms constructed for predicting the efficacy and prognosis of advanced non­small cell lung cancer patients treated with anti­PD­1 inhibitors based on the absolute counts of lymphocyte subsets.

BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.

Global availability of parenteral nutrition: Pre- and post-COVID-19 pandemic surveys.

OBJECTIVE: Parenteral nutrition represents a therapeutic option for patients with type 3 intestinal failure. If used exclusively, parenteral nutrition has to be complete to provide all essential nutrients. The aim was to assess the availability of parenteral nutrition in all parts of the world, to better comprehend the global situation, and to prepare an action plan to increase access to parenteral nutrition. METHODS: An international survey using an electronic questionnaire was conducted in August 2019 and repeated in May 2022. An electronic questionnaire was sent to 52 members or affiliates of the International Clinical Nutrition Section of the American Society for Parenteral and Enteral Nutrition. Questions addressed the availability of parenteral nutrition admixtures and their components, reimbursement, and prescribing pre- and post-COVID-19 pandemic. All participating countries were categorized by their economic status. RESULTS: Thirty-six country representatives responded, answering all questions. Parenteral nutrition was available in all countries (100%), but in four countries (11.1%) three-chamber bags were the only option, and in six countries a multibottle system was still used. Liver-sparing amino acids were available in 18 (50%), kidney-sparing in eight (22.2%), and electrolyte-free in 11 (30.5%) countries (30.5%). In most countries (n = 28; 79.4%), fat-soluble and water-soluble vitamins were available. Trace elements solutions were unavailable in four (11.1%) countries. Parenteral nutrition was reimbursed in most countries (n = 33; 91.6%). No significant problems due to the coronavirus pandemic were reported. CONCLUSIONS: Despite the apparent high availability of parenteral nutrition worldwide, there are some factors that may have a substantial effect on the quality of parenteral nutrition admixtures. These shortages create an environment of inequality.

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).

Immune signature and phagocytosis of circulating DC subsets in healthy adults during aging.

Dendritic cells (DC) play a pivotal role in the onset and progression of immunosenescence-associated diseases, serving as a link between innate and adaptive immunity. Thus, there is a need to establish reference ranges for DC subset levels in healthy adults and investigate the potential impact of age on DC subset levels and phagocytic activity. Single-platform multi-color flow cytometry was performed to assess the proportions of circulating conventional type 1 DC (cDC1), conventional type 2 DC (cDC2), and plasmacytoid DC (pDC), as well as the percentages of CD80, CD86, CD83, PD-L1, and CD32 in cDC1, cDC2, and pDC. Reference ranges were established based on age and gender, and the percentage of circulating DC subsets in different age groups was compared. In addition, circulating DC were enriched using a magnetic bead sorting kit and co-cultured with polystyrene (PS) beads, categorized by age groups, followed by the evaluation of PS bead phagocytosis using light microscopy and flow cytometry. The results indicated that the percentages of circulating cDC1, cDC2, and CD32+cDC2 decreased with age (P < 0.05) and revealed age-related impairment in phagocytic percentage of cDC2 (P < 0.05). These findings provide a deeper understanding of the impact of age on the phenotype and phagocytic activity of DC subsets, shedding light on their role and function in immunosenescence.

7,8-dihydroxyflavone displayed antioxidant effect through activating HO-1 expression and inhibiting caspase-3/PARP activation in RAW264.7 cells.

Flavonoids, which contain a benzo-γ-pyrone (C6-C3-C6) skeleton, have been reported to exhibit effective antioxidant ability. This study aimed to compare the antioxidant activities of 7,8-dihydroxyflavone (7,8-DHF) and 7-hydroxyflavone (7-HF) in H2 O2 , lipopolysaccharide (LPS), or tert-butyl hydroperoxide (t-BHP)-induced RAW264.7 cells, respectively. The antioxidant capacities of 7,8-DHF and 7-HF were firstly evaluated by 2,2-azinobis-3-ethyl-benzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Then, reactive oxygen species (ROS), super oxide dismutase (SOD), and malondialdehyde (MDA) productions in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells were tested and compared, respectively. Finally, the antioxidant mechanisms of 7-HF and 7,8-DHF were initially investigated by western blot. Our results showed that 7,8-DHF possessed stronger free-radical scavenging capacity than 7-HF. Both 7,8-DHF and 7-HF suppressed MDA production and ROS accumulation, improved the activity of SOD in H2 O2 , LPS, or t-BHP-induced RAW264.7 cells, respectively. And 7,8-DHF exerted a better antioxidant effect than 7-HF, especially in t-BHP-induced oxidative stress. Mechanically, 7,8-DHF prevented the activation of poly ADP-ribosepolymerase and caspase-3, meanwhile markedly upregulated the expression of HO-1 protein in t-BHP-induced oxidative stress. These results suggested that 7,8-DHF might serve as a potential pharmaceutical drug against oxidative stress injury.

The DC-T cell axis is an effective target for the treatment of non-small cell lung cancer.

The dendritic cell (DC)-T cell axis is a bridge that connects innate and adaptive immunities. The initial immune response against tumors is mainly induced by mature antigen-presenting DCs. Enhancing the crosstalk between DCs and T cells may be an effective approach to improve the immune response to non-small cell lung cancer (NSCLC). In this article, a review was made of the interaction between DCs and T cells in the treatment of NSCLC and how this interaction affects the treatment outcome.

Prognostic significance of blood-based PD-L1 analysis in patients with non-small cell lung cancer undergoing immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

BACKGROUND: The main types of PD-L1 in the blood include soluble PD-L1 (sPD-L1), exosomal PD-L1 (exoPD-L1), and PD-L1 in circulating tumor cells (CTCs). However, the predictive and prognostic values of these three indicators in patients with non-small cell lung cancer (NSCLC) undergoing immune checkpoint inhibitor (ICI) therapy are unclear, warranting a systematic meta-analysis. METHODS: A systematic literature search was performed in the PubMed, Cochrane Library, and Embase databases. The pooled hazard ratio (HR) and 95% confidence interval (CI) values were extracted from the included studies to investigate the correlation between the three PD-L1 indicators and overall survival (OS) or progression-free survival (PFS). The Newcastle-Ottawa Scale (NOS) was used to examine the quality of the included studies. Subgroup analyses were employed to investigate the heterogeneity. The publication bias of the included studies was assessed using Begg's and Egger's tests. P < 0.05 was regarded as significantly different. RESULTS: The pooled results revealed that high pre-treatment sPD-L1 levels were significantly associated with inferior OS (HR = 2.32, 95% CI = 1.68-3.18, P < 0.001) and PFS (HR = 2.52, 95% CI = 1.72-3.68, P < 0.001). However, dynamic changes in sPD-L1 after immunotherapy were not statistically significant for OS (HR = 1.46, 95% CI = 0.65-3.26, P > 0.05) or PFS (HR = 1.62, 95% CI = 0.92-2.86, P > 0.05). Meanwhile, the upregulated pre-treatment exoPD-L1 levels were significantly associated with poor PFS (HR = 4.44, 95% CI = 2.87-6.89, P < 0.001), whereas the post-treatment dynamic upregulation of exoPD-L1 was significantly correlated with superior PFS (HR = 0.36, 95% CI = 0.24-0.54, P < 0.001) and OS (HR = 0.20, 95% CI = 0.07-0.53, P < 0.001). For PD-L1 in CTCs, the pooled results indicated that PD-L1 expression in CTCs was not significantly correlated with OS (HR = 0.75, 95% CI = 0.49-1.13, P = 0.170) and PFS (HR = 0.79, 95% CI = 0.59-1.06, P = 0.12). CONCLUSIONS: Blood-based PD-L1 analysis is a potential strategy for predicting treatment efficacy and prognosis in patients with cancer.

Perioperative chemotherapy versus adjuvant chemotherapy treatment for resectable locally advanced gastric cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS: Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS: Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.

Antibacterial metabolites from the beetle-associated fungus Penicillium chrysogenum.

The antibacterial secondary metabolites of the fungus Penicillium chrysogenum associated with the beetle Aspongopus chinensis were investigated through chromatographic fractionation methods of ethyl acetate extracts of the fungal cultures. Five compounds were isolated, and their structures were determined as emodin, 4-(methoxymethyl)benzoic acid, isoochracinic acid, secalonic acid D, and dicerandrol A using mass spectroscopy and nuclear magnetic resonance spectroscopic analyses. Emodin exhibited strong antimicrobial activity, especially against Staphylococcus aureus even when growing on cooked pork, with a minimal inhibitory concentration (MIC) of 6.3 µg/mL. Dimeric tetrahydroxanthones, such as secalonic acid D and dicerandrol A, also exhibited potent activity, with MIC values ranging from 9.5 to 28.5 µg/mL. In summary, P. chrysogenum was isolated as a symbiotic fungus of the beetle A. chinensis for the first time and this strain could generate antibacterial secondary metabolites, which could potently inhibit gram-positive bacteria growth in vitro.

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).

Identification of SPRYD4 as a tumour suppressor predicts prognosis and correlates with immune infiltration in cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive solid tumour with a 5-year survival rate ranging from 7% to 20%. It is, therefore, urgent to identify novel biomarkers and therapeutic targets to improve the outcomes of patients with CCA. SPRY-domain containing protein 4 (SPRYD4) contains SPRY domains that modulate protein-protein interaction in various biological processes; however, its role in cancer development is insufficiently explored. This study is the first to identify that SPRYD4 is downregulated in CCA tissues using multiple public datasets and a CCA cohort. Furthermore, the low expression of SPRYD4 was significantly associated with unfavourable clinicopathological characteristics and poor prognosis in patients with CCA, indicating that SPRYD4 could be a prognosis indicator of CCA. In vitro experiments revealed that SPRYD4 overexpression inhibited CCA cells proliferation and migration, whereas the proliferative and migratory capacity of CCA cells was enhanced after SPRYD4 deletion. Moreover, flow cytometry showed that SPRYD4 overexpression triggered the S/G2 cell phase arrest and promoted apoptosis in CCA cells. Furthermore, the tumour-inhibitory effect of SPRYD4 was validated in vivo using xenograft mouse models. SPRYD4 also showed a close association with tumour-infiltrating lymphocytes and important immune checkpoints including PD1, PD-L1 and CTLA4 in CCA. In conclusion, this study elucidated the role of SPRYD4 during CCA development and highlighted SPRYD4 as a novel biomarker and tumour suppressor in CCA.

Sacubitril/valsartan: research progress of multi-channel therapy for cardiorenal syndrome.

Cardiorenal syndrome (CRS) results from complex interaction between heart and kidneys, inducing simultaneous acute or chronic dysfunction of these organs. Although its incidence rate is increasing with higher mortality in patients, effective clinical treatment drugs are currently not available. The literature suggests that renin-angiotensin-aldosterone system (RAAS) and diuretic natriuretic peptide (NP) system run through CRS. Drugs only targeting the RAAS and NPs systems are not effective. Sacubitril/valsartan contains two agents (sacubitril and valsartan) that can regulate RAAS and NPs simultaneously. In the 2017 American College of Cardiology/American Heart Association/American Heart Failure (HF) ssociation (ACC/AHA/HFSA) guideline, sacubitril/valsartan was recommended as standard therapy for HF patients. The latest research shows that Combined levosimendan and Sacubitril/Valsartan markets are protected the heart and kidney against cardiovascular syndrome in rat. However, fewer studies have reported its therapeutic efficacy in CRS treatment, and their results are inconclusive. Therefore, based on RAAS and NPs as CRS biomarkers, this paper summarizes possible pathophysiological mechanisms and preliminary clinical application effects of sacubitril/valsartan in the prevention and treatment of CRS. This will provide a pharmacological justification for expanding sacubitril/valsartan use to the treatment of CRS.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. METHODS: Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (-) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194-0.468, p = 0.002). Multivariable Cox regression analysis identified that lymph node status after NACT was an independent prognostic factor associated with survival (OS: hazard ratio 1.756, 95% CI 1.114-3.278, p = 0.029; DFS: hazard ratio 1.901, 95% CI 1.331-3.093, p = 0.012). CONCLUSION: Lymph node status is a potential independent prognostic factor for LAGC patients treated with NACT and may be more efficient than pathological response in primary tumor.

Comparisons of nutritional status and complications between patients with and without postoperative feeding jejunostomy tube in gastric cancer: a retrospective study.

Background: Feeding jejunostomy tube (FJT) enables early postoperative nutritional supply for gastric cancer patients undergoing surgery. However, the nutritional benefit of FJT may be accompanied by potential risk of increased complications, so both the nutritional improvement and the complication rates associated with FJT should be assessed. Methods: From January 2009 to December 2014, 715 consecutive patients underwent gastric cancer resection at the Peking Union Medical College Hospital in China. The perioperative nutritional index and incidence of complications in patients with FJT placement were retrospectively compared to those in patients without FJT placement. Nutritional data including albumin, prealbumin, hemoglobin, and high sensitivity C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutrition index (OPNI) were recorded at the following 3 timepoints: preoperatively, 1-week postoperatively, and 1-month postoperatively. Postoperative complications including surgical site infection, intra-abdominal infections, anastomotic leaks and gastroparesis were assessed. Multivariate logistic regression was used to study the association between FJT and complications. Results: A total of 715 patients were included in the study. The mean age was 60.4 years and 72.2% were male. The overall characteristics between FJT and no-FJT groups were comparable. Of the 247 total gastrectomy cases, 98 (39.7%) had a FJT placed. Compared to the total gastrectomy patients without a FJT, the 98 patients with a FJT had a lower hemoglobin level (P=0.048) and NLR (P=0.030) preoperatively, and higher albumin (P=0.005), prealbumin (P<0.001), and hemoglobin (P=0.014) levels, a higher OPNI (P=0.027), and a lower NLR (P=0.005) 1-month postoperatively. Of the 468 subtotal gastrectomy cases, 87 (18.6%) had a FJT placed. Compared to the subtotal gastrectomy patients without a FJT, these 87 patients had a lower NLR (P=0.006) 1-week postoperatively, and a higher albumin level (P=0.009) 1-month postoperatively. In the multivariate analysis, FJT placement was not associated with postoperative adverse outcomes, including surgical site infection [odds ratio (OR) =1.21, P=0.79], intra-abdominal infection (OR =0.38, P=0.11), anastomotic leak (OR =0.58, P=0.53), reoperation (OR =0.22, P=0.23), gastroparesis (OR =6.35, P=0.08), or hospitalization for more than 30 days (OR =0.58, P=0.32). Conclusions: Early enteral nutritional support by FJT after gastrectomy tended to improve the nutritional status of patients, while it did not appear to increase the incidence rate of postoperative complications.

Association between Plasma FGF21 Levels and Body Composition in Patients with Gastric Cancer.

BACKGROUND: Accumulating evidence has suggested that Fibroblast growth factor 21 (FGF21) plays an important role in metabolic diseases. This study aimed to investigate the relationship between plasma FGF21 levels and body composition parameters in gastric cancer (GC) patients. METHODS: This study was cross-sectional based on a prospective cohort of GC patients in a single center. Computer tomography (CT) and bioelectrical impedance analysis (BIA) were used to estimate skeletal muscle and adipose tissue mass. Blood samples were collected and plasma concentrations of FGF21 were measured by ELISA. Spearman's rank correlation test and logistic regression analysis were performed to assess associations between plasma FGF21 levels and these body composition parameters. RESULTS: A total of 66 GC patients were enrolled in this study. Plasma FGF21 levels were significantly higher in women compared with men. The plasma FGF21 levels were positively correlated with fat mass index (FMI), fat mass percentage (FM%), and subcutaneous adipose tissue index (SATI). Furthermore, after adjustment for confounders, the lower plasma FGF21 levels were remain associated with increased odds for low SATI. CONCLUSIONS: Plasma FGF21 levels were positively associated with FMI, FM%, and SATI in GC patients, suggesting a potential mechanistic link between FGF21 and subcutaneous adipose tissue in GC.

Intestinal Nutrition Played a Vital Important Role in an Intestinal Perforation Patient with Chronic Constipation: A Case Report.

Introduction: Nutrition treatment is important in the critically ill patient. Nutritional therapy should be instituted as soon as possible if indicated. Case presentation: A 64-year-old woman with malnutrition and intestinal obstruction with gastrointestinal bleeding came to our emergency room. She had a history of constipation. After CT scan, we found perforations in the digestive tract. Because she could not tolerate surgery and parenteral nutrition (PN), we chose to start enteral nutrition (EN). She recovered after the initiation of EN. Discussion: Chronic constipation may cause intestinal obstruction, which is rare but fatal. Providers should evaluate the nutritional status for the intensive care patient and start PN/EN at once if necessary. EN may help the closure of perforations. Conclusion: EN may play a vital important role even in the patients who have perforations in the digestive tract. Chronic constipation may cause obstruction and perforation, which are rare but fatal.

Urolithin A suppresses tumor progression and induces autophagy in gastric cancer via the PI3K/Akt/mTOR pathway.

Urolithin A (UA) is a microbial metabolite of natural polyphenols ellagitannins and ellagic acid with well-established antitumor properties against various malignancies. However, the exact role of UA in gastric cancer (GC) progression remains largely unclear. In the present study, we investigated the effects and potential mechanisms of UA in GC in vitro and in vivo. Our results revealed that UA could suppress GC cell proliferation, inhibit migration and invasion, promote apoptosis, and induce autophagy via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway in vitro. The autophagy inhibitors 3-methyladenine and chloroquine augmented the inhibitory effect of UA on proliferation and promoted apoptosis, implying that UA mediated the cytoprotective role of autophagy. Meanwhile, the in vivo experiments showed that UA effectively suppressed tumor growth, enhanced the therapeutic effects, and alleviated chemotherapy toxicity in xenograft models. Overall, these findings offer novel insights into the role of UA in tumor therapy and suggest that UA may possess potential therapeutic applications for GC.