Association between dietary folate intake and severe abdominal aorta calcification in adults: A cross-sectional analysis of the national health and nutrition examination survey.

BACKGROUND: Prior studies have established a connection between folate intake and cardiovascular disease (CVD). Abdominal aortic calcification (AAC) has been introduced as a good predictor of CVD events, but no previous study has investigated the relationship between dietary folate intake and severe AAC. Therefore, the study aims to explore the association between dietary folate intake and severe AAC in the United States (US) middle-aged and elderly population. METHODS: This study employed cross-sectional data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) to examine the relationship between dietary folate intake and severe AAC. Two 24-h dietary recall interviews were conducted to assess dietary folate intake and its sources, while a DXA scan was used to determine the AAC score. To analyze the association between dietary folate intake and severe AAC, a multivariable logistic regression model was applied, and a subgroup analysis was performed. RESULTS: Our analysis utilized data from 2640 participants aged 40 years and above, including 288 individuals diagnosed with severe AAC. After adjusting for confounding factors, we observed an inverted L-shaped association between folate intake and severe AAC. Upon further adjustment for specific confounding factors and covariates, the multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the second, third, and fourth quartiles of folate intake, using the first quartile as the reference, were as follows: 1.24 (0.86-1.79), 0.86 (0.58-1.27), and 0.63 (0.41-0.97), respectively. Subgroup analysis results were consistent with the logistic regression models, indicating concordant findings. Moreover, no significant interaction was observed in the subgroup analyses. CONCLUSIONS: The study findings suggest an inverted L-shaped association between dietary folate intake and severe AAC. However, additional prospective investigations are necessary to explore the impact of dietary folate intake on severe AAC in patients.

U-Shaped Association between Serum Chloride Levels and In-Hospital Mortality in Patients with Congestive Heart Failure in Intensive Care Units.

Serum chloride level has clinical significance in the prognosis of heart failure. Little is known regarding the association between serum chloride levels and in-hospital mortality in patients with heart failure.This retrospective study used clinical data obtained from the Medical Information Mart for Intensive Care Database. The study cohort comprised patients who were categorized on the basis of their serum chloride levels, and the primary endpoint was in-hospital mortality. To assess the impact of serum chloride levels at the time of intensive care unit admission on in-hospital mortality, we used various statistical approaches, including multivariable logistic regression models, a generalized additive model, and a two-piecewise linear regression model. In addition, subgroup analysis was conducted to examine the robustness of the main findings.This study comprised 15,983 participants. When compared with the reference group (Q5), the groups with the highest (Q7) and lowest (Q1) blood chloride levels exhibited increased in-hospital mortality, with fully adjusted odds ratios (ORs) of 1.36 [95% confidence interval (CI): 1.08-1.71] and 1.25 (95% CI: 1-1.56), respectively. A U-shaped relationship was observed between blood chloride levels and in-hospital mortality, with the lowest risk observed at a threshold of 105.017 mmol/L. The effect sizes and corresponding CIs below and above the threshold were 0.969 (95% CI: 0.957-0.982) and 1.039 (95% CI: 1.002-1.076), respectively. Stratified analyses demonstrated the robustness of this correlation.The relationship between serum chloride levels and in-hospital mortality in patients with heart failure was U-shaped, with an inflection point of 105.017 mmol/L.

U-shaped association between serum calcium and in-hospital mortality in patients with congestive heart failure.

AIMS: Serum calcium level is widely used for evaluating disease severity, but its impact on clinical outcomes in patients with congestive heart failure (CHF) remains poorly understood. The aim of this study is to investigate the relationship between serum calcium levels and in-hospital mortality in CHF patients. METHODS AND RESULTS: We conducted a retrospective analysis utilizing clinical data from the Medical Information Mart for Intensive Care database, encompassing a cohort of 15 983 CHF patients. This cohort was stratified based on their serum calcium levels, with the primary objective being the determination of in-hospital mortality. To assess the impact of admission serum calcium levels on in-hospital mortality, we employed various statistical methodologies, including multivariable logistic regression models, a generalized additive model, a two-piecewise linear regression model, and subgroup analysis. Comparative analysis of the reference group (Q3) revealed increased in-hospital mortality in the first quintile (Q1, the group with the lowest blood calcium level) and the fifth quintile (Q5, the group with the highest blood calcium level), with fully adjusted odds ratios of 1.38 [95% confidence interval (CI): 1.13-1.68, P = 0.002] and 1.23 (95% CI: 1.01-1.5, P = 0.038), respectively. A U-shaped relationship was observed between serum calcium levels and in-hospital mortality, with the lowest risk occurring at a threshold of 8.35 mg/dL. The effect sizes and corresponding CIs below and above this threshold were 0.782 (95% CI: 0.667-0.915, P = 0.0023) and 1.147 (95% CI: 1.034-1.273, P = 0.0094), respectively. Stratified analyses confirmed the robustness of this correlation. CONCLUSIONS: Our study identifies a U-shaped association between serum calcium levels and in-hospital mortality in CHF patients, with a notable inflection point at 8.35 mg/dL. Further investigation through prospective, randomized, and controlled studies is warranted to validate the findings presented in this study.

Association between dietary calcium intake and severe abdominal aorta calcification among American adults: a cross-sectional analysis of the National Health and Nutrition Examination Survey.

BACKGROUND: Evidence regarding the relationship between dietary calcium intake and severe abdominal aortic calcification (AAC) is limited. Therefore, this study aimed to investigate the association between dietary calcium intake and severe AAC in American adults based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The present cross-sectional study utilized data from the NHANES 2013-2014, a population-based dataset. Dietary calcium intake was assessed using two 24-h dietary recall interviews. Quantification of the AAC scores was accomplished utilizing the Kauppila score system, whereby severe AAC was defined as having an AAC score greater than 6. We used multivariable logistic regression models, a restricted cubic spline analysis, and a two-piecewise linear regression model to show the effect of calcium intake on severe AAC. RESULTS: Out of the 2640 individuals examined, 10.9% had severe AAC. Following the adjustment for confounding variables, an independent association was discovered between an augmented intake of dietary calcium and the incidence of severe AAC. When comparing individuals in the second quartile (Q2) of dietary calcium intake with those in the lowest quartile (Q1), a decrease in the occurrence of severe AAC was observed (odds ratio: 0.66; 95% confidence interval: 0.44-0.99). Furthermore, the relationship between dietary calcium intake and severe AAC demonstrated an L-shaped pattern, with an inflection point observed at 907.259 mg/day. Subgroup analyses revealed no significant interaction effects. CONCLUSION: The study revealed that the relationship between dietary calcium intake and severe AAC in American adults is L-shaped, with an inflection point of 907.259 mg/day. Further research is required to confirm this association.

Association between dietary total choline and abdominal aorta calcification among older US adults: A cross-sectional study of the National Health and Nutrition Examination Survey.

BACKGROUND: Numerous studies indicate a potential bidirectional association between dietary choline intake and its derivative, betaine, and subclinical atherosclerosis. However, little research has been conducted on the relationship between dietary choline and severe abdominal aortic calcification (SAAC). METHODS: This cross-sectional study analyzed population-based data from the National Health and Nutrition Examination Survey (2013-2014). Choline intake and food sources were measured using two 24-h dietary-recall interviews. The abdominal aortic calcification score was measured using a dual-emission x-ray absorptiometry scan. To assess the relationship between choline intake and SAAC, the study utilized restricted cubic spline and a multivariable logistic regression model. RESULTS: Among the 2640 individuals included in the study, 10.9% had SAAC. After adjusting for all selected covariates, compared with the lowest quartile of dietary choline, the odds ratios of SAAC for the second-quartile, third-quartile, and fourth-quartile dietary choline intake were 0.63 (95% confidence interval [CI], 0.43-0.93), 0.63 (95% CI, 0.42-0.94), and 0.77 (95% CI, 0.5-1.16), respectively. The study found an L-shaped relationship between dietary choline and SAAC in the dose-response analysis. Subgroup analyses did not demonstrate any statistically significant interaction effects for any subgroup. CONCLUSION: The study found that a higher intake of dietary choline is associated with a lower prevalence of SAAC. The dose-response analysis revealed an L-shaped relationship between dietary choline and SAAC. However, further studies are warranted to investigate the direct role of choline in the development of SAAC.

Association Between Body Temperature and In-Hospital Mortality Among Congestive Heart Failure Patients with Diabetes in Intensive Care Unit: A Retrospective Cohort Study.

Body temperature (BT) has been utilized to assess patient outcomes across various diseases. However, the impact of BT on mortality in the intensive care unit (ICU) among patients with congestive heart failure (CHF) and diabetes mellitus (DM) remains unclear. We conducted a retrospective cohort study using data from the Medical Information Mart for Intensive Care (MIMIC)-IV data set. The primary outcome assessed was in-hospital mortality rates. BT was treated as a categorical variable in the analyses. The association between BT on ICU admission and in-hospital mortality was examined using multivariable logistic regression models, restricted cubic spline, and subgroup analysis. The cohort comprised 7063 patients with both DM and CHF (3135 females and 3928 males), with an average age of 71.5 ± 12.2 years. Comparative analysis of the reference group (Q4) revealed increased in-hospital mortality in Q6 and Q1 temperature groups, with fully adjusted odds ratios of 2.08 (95% confidence interval [CI]: 1.45-2.96) and 1.95 (95% CI: 1.35-2.79), respectively. Restricted cubic spline analysis demonstrated a U-shaped relationship between temperature on admission and mortality risk (p nonlinearity <0.001), with the nadir of risk observed at 36.8°C. The effect sizes and corresponding CIs below and above the threshold were 0.581 (95% CI: 0.434-0.777) and 1.674 (95% CI: 1.204-2.328), respectively. Stratified analyses further validated the robustness of this correlation. Our study establishes a nonlinear association between BT and in-hospital mortality in patients with both CHF and DM, with optimal suitable BT at 36.8°C. Further research is necessary to confirm this relationship.

Association between dietary zinc intake and Helicobacter pylori seropositivity in US adults: National Health and Nutrition Examination Survey.

Purpose: Helicobacter pylori infection is a well-established etiological factor for gastric inflammation and a significant risk factor for the development of gastric cancer. However, the precise relationship between dietary zinc intake and seropositivity for Helicobacter pylori remains uncertain. Methods: This cross-sectional observational study utilized data from the United States National Health and Nutrition Examination Survey conducted between 1999 and 2000. The study cohort comprised 2,884 adults aged 20 years or older who provided comprehensive 24-h dietary recall data. The presence of Helicobacter pylori infection was confirmed using serum analysis and lgG protein enzyme-linked immunosorbent assay (ELISA). Multivariable logistic regression models and generalized additive model (GAM) were employed to explore the potential association between dietary zinc intake and Helicobacter pylori seropositivity. Results: Additionally, subgroup analysis was performed to evaluate the robustness of the primary findings. Of the 1,281 participants, 47.8% were male and the average age was 49.5 years. In the fully adjusted model, a statistically significant inverse association between dietary zinc intake and Helicobacter pylori seropositivity was observed [quartile variable, Q4 vs. Q1, odds ratio (OR): 0.72, 95% confidence interval (CI): 0.57-0.91, p = 0.007]. Furthermore, the relationship between dietary zinc intake and Helicobacter pylori seropositivity exhibited an L-shaped pattern, indicating a saturation effect. The results of sensitivity analysis remained consistent and reliable. Conclusion: Therefore, this study suggests that higher dietary zinc intake may be associated with a lower prevalence of Helicobacter pylori seropositivity. Notably, this association follows an L-shaped pattern, with a threshold point estimated at 24.925 mg/day.

Association between dietary vitamin E intake and cognitive decline among old American: National Health and Nutrition Examination Survey.

PURPOSE: Numerous studies have reported that vitamin E plays a key role in nervous system development and neurotransmitter production. This study aimed to investigate changes in vitamin E intake in older adults with low cognitive performance using NHANES. METHODS: In this cross-sectional study, we examined a sample of 2255 American adults aged 60 and over between 2011 and 2014. We collected dietary data by averaging two recalls for dietary use to determine vitamin E intake. We assessed cognitive function using five tests and analyzed the association between these variables using a multivariate logistic regression model. RESULTS: A total of 2255 participants aged ≥ 60 years from the National Health and Nutrition Examination Survey (NHANES) for the 2011-2014 cycle were included in the analysis. Vitamin E intake was negatively associated with cognitive function. In the Z test, with each 1 mg/day increase in dietary intake of vitamin E, there was a 6% decrease in the correlation with cognitive impairment (OR = 0.94, 95% CI 0.91-0.97) in the fully fitted model (OR = 0.94, 95% CI 0.91-0.97). These findings remained consistent when analyzing the exposure as a categorical variable. In comparison to Q1, Q4 showed a 53% reduction in the incidence of cognitive impairment in the Z test (OR = 0.47, 95% CI 0.33-0.67).No significant statistical interaction between the variables was found. CONCLUSION: An increased dietary intake of vitamin E has been associated with decreased cognitive impairment in individuals over 60 years old. The dose-response curve showed an L-shaped association between dietary vitamin E intake and cognitive decline in US adults, with an inflection point of approximately 9.296 mg/day.

Recent advances in biomimetic hemostatic materials.

Although the past decade has witnessed unprecedented medical advances, achieving rapid and effective hemostasis remains challenging. Uncontrolled bleeding and wound infections continue to plague healthcare providers, increasing the risk of death. Various types of hemostatic materials are nowadays used during clinical practice but have many limitations, including poor biocompatibility, toxicity and biodegradability. Recently, there has been a burgeoning interest in organisms that stick to objects or produce sticky substances. Indeed, applying biological adhesion properties to hemostatic materials remains an interesting approach. This paper reviews the biological behavior, bionics, and mechanisms related to hemostasis. Furthermore, this paper covers the benefits, challenges and prospects of biomimetic hemostatic materials.

Microbiota-derived short-chain fatty acids and modulation of host-derived peptides formation: Focused on host defense peptides.

The byproducts of bacterial fermentation known as short-chain fatty acids (SCFAs) are chemically comprised of a carboxylic acid component and a short hydrocarbon chain. Recent investigations have demonstrated that SCFAs can affect intestinal immunity by inducing endogenous host defense peptides (HDPs) and their beneficial effects on barrier integrity, gut health, energy supply, and inflammation. HDPs, which include defensins, cathelicidins, and C-type lectins, perform a significant function in innate immunity in gastrointestinal mucosal membranes. SCFAs have been demonstrated to stimulate HDP synthesis by intestinal epithelial cells via interactions with G protein-coupled receptor 43 (GPR43), activation of the Jun N-terminal kinase (JNK) and Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, and the cell growth pathways. Furthermore, SCFA butyrate has been demonstrated to enhance the number of HDPs released from macrophages. SCFAs promote monocyte-to-macrophage development and stimulate HDP synthesis in macrophages by inhibiting histone deacetylase (HDAC). Understanding the etiology of many common disorders might be facilitated by studies into the function of microbial metabolites, such as SCFAs, in the molecular regulatory processes of immune responses (e.g., HDP production). This review will focus on the current knowledge of the role and mechanism of microbiota-derived SCFAs in influencing the synthesis of host-derived peptides, particularly HDPs.

Association between dietary folate intake and cognitive impairment in older US adults: National Health and Nutrition Examination Survey.

OBJECTIVE: To determine the association between dietary folate intake and low cognitive performance in older adults. METHODS: In this cross-sectional observational study, 2011-2014 data from the 2010 National Health and Nutrition Examination Survey, including 2,524 adults aged 60 years and older, included 24-hour dietary intakes. Total folic acid intake was calculated as the sum of folic acid supplements and dietary folic acid. Cognitive function was assessed using three tests. The association between folate intake and cognitive function was assessed using a multivariate conditional logistic regression model. RESULTS: 2524 participants from two survey cycles (2011-2014) in the NHANES aged 60 years and over. In the multivariate logistic regression, the OR of developing folate was 0.96 (95% CI: 0.94∼0.98) in participants with Z test. Folate intake was negatively associated with cognitive function. Compared with Q1, Q4(≥ 616.3mg/day) in the AFT and DSST tests reduced the risk of cognitive impairment by 31% (OR = 0.69, 95% CI: 0.52-0.93) and 44% (OR = 0.56). 95% confidence interval: 0.44-0.7). In the comprehensive evaluation of IR and AFT scores, the association between dietary folate intake and low cognitive performance in US adults is linear. We also found a significant interaction between gender and cognitive ability (P value for the interaction was 0.021). CONCLUSIONS: Dietary intake of folic acid may be inversely associated with cognitive impairment. The DSST study found an L-shaped association between dietary folate intake and cognitive decline in US adults, with an inflection point of approximately 510,383 mg/day.

Functional and clinical characteristics of focal adhesion kinases in cancer progression.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase and an adaptor protein that primarily regulates adhesion signaling and cell migration. FAK promotes cell survival in response to stress. Increasing evidence has shown that at the pathological level, FAK is highly expressed in multiple tumors in several systems (including lung, liver, gastric, and colorectal cancers) and correlates with tumor aggressiveness and patient prognosis. At the molecular level, FAK promotes tumor progression mainly by altering survival signals, invasive capacity, epithelial-mesenchymal transition, the tumor microenvironment, the Warburg effect, and stemness of tumor cells. Many effective drugs have been developed based on the comprehensive role of FAK in tumor cells. In addition, its potential as a tumor marker cannot be ignored. Here, we discuss the pathological and pre-clinical evidence of the role of FAK in cancer development; we hope that these findings will assist in FAK-based clinical studies.

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis.

Objective: The progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated. Methods: Original articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis. Results: In total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44-0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25-0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09-0.22) and 0.86 (95% CI: 0.83-0.89), respectively. Conclusion: Neoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.

Case Report: Clostridial Gas Gangrene of Pelvic Wall After Laparoscopic Rectal Cancer Surgery Induced Fatal Sepsis.

Clostridial gas gangrene is an unusual but fast-spreading necrotic infection of soft tissue relevant to high mortality rates. We report a case of postoperative gas gangrene of the pelvic wall, scrotum, and perineal site, with very acute onset and rapid progression of symptoms after laparoscopic radical resection for rectal cancer. Although potentially treatable with appropriate antibiotic cover and urgent thorough surgical debridement, this case still developed irreversibly into fulminant and fatal sepsis. The possible etiologic factors, better measures of diagnosis, and treatment are discussed, and the relevant literature is reviewed.

CHSY1 is upregulated and acts as tumor promotor in gastric cancer through regulating cell proliferation, apoptosis, and migration.

Gastric cancer is one of the most frequently diagnosed malignant tumors, with rapid progression and poor prognosis. The role of chondroitin sulfate synthase 1 (CHSY1) in the development and progression of gastric cancer was explored and clarified in this study. The immunohistochemistry analysis of clinical tissue samples as well as data mining of public database showed that CHSY1 was significantly upregulated in gastric cancer and associated with more advanced tumor stage and poorer prognosis. In vitro loss-of-function experiments demonstrated the inhibited cell proliferation, colony formation, cell migration, as well as the promoted cell apoptosis by CHSY1 knockdown. Moreover, recovery of CHSY1 expression could attenuate the regulatory effects induced by CHSY1 knockdown. Correspondingly, gastric cancer cells with CHSY1 knockdown showed reduced tumorigenicity and slower tumor growth in vivo. In conclusion, this study identified CHSY1 as a tumor promotor in gastric cancer, which may be utilized as a novel indicator of patients' prognosis and therapeutic target for developing more effective drug for GC treatment.

Overexpression of long non-coding RNA RP11-363E7.4 inhibits proliferation and invasion in gastric cancer.

LncRNA RP11-363E7.4 has been shown to be downregulated in gastric cancer (GC), while the effect of lncRNA RP11-363E7.4 on GC and its potential molecular mechanisms is unclear. The purpose of this study was to explore the functional role and underlying molecular mechanisms of lncRNA RP11-363E7.4 involved in GC progress.To address the question, quantitative real-time PCR assay was performed to confirm lncRNA RP11-363E7.4 expression levels in GC tissues and cell lines. Cell proliferation, apoptosis, migration and invasion were estimated using Cell Counting Kit-8, colony formation, scratch wound healing and Transwell assays. Potential molecular mechanisms were evaluated using western blot assay. The results showed that lncRNA RP11-363E7.4 was significantly downregulated in GC cell lines and 82 paired tissues. The correlation between expression and clinicopathological features indicated that low expression of lncRNA RP11-363E7.4 was associated with T stage (P = .010). Functional experiments showed that overexpression of lncRNA RP11-363E7.4 prevented proliferation, migration, and invasion and induced apoptosis of GC cells. Western blot assay revealed that lncRNA RP11-363E7.4 functioned via the p53, Bax/Bcl-2, ß-catenin pathway. In summary, this study revealed that lncRNA RP11-363E7.4 functioned as a tumour suppressor by inhibiting proliferation, migration, and invasion and inducing apoptosis of GC cells. Significance of the study:LncRNA RP11-363E7.4 has been shown to be downregulated in GC, while the effect of lncRNA RP11-363E7.4 on GC and its potential molecular mechanism is unclear. We revealed that lncRNA RP11-363E7.4 functioned as a tumour suppressor by inhibiting proliferation, migration, and invasion and inducing apoptosis of GC cells. LncRNA RP11-363E7.4 might become an attractive diagnostic and prognostic biomarker of GC and a promising target for GC treatment.

Current Understanding of Circular RNAs in Gastric Cancer.

Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Advanced diagnosis and high rates of relapse and metastasis are associated with the poor prognosis of this disease. GC has a complex etiopathogenesis of which the underlying mechanisms remain to be explored. Studies on circular RNAs (circRNAs), noncoding RNAs that may be potential targets in GC, have made substantial progress over the past few years. CircRNAs exert important effects on the onset and progression of GC. Hence, this article aims to summarize the findings of recent studies of circRNAs related to GC and to describe the underlying mechanisms and potential applications. The findings indicate that circRNAs participate in GC regulation, proliferation, invasion, and metastasis through regulating microRNAs, proteins, genes, and signaling pathways. In addition, dysregulated circRNAs may be used as novel diagnostic and prognostic biomarkers or therapeutic targets. This review is expected to facilitate a better understanding of GC, and it suggests novel circRNA-based methods to inhibit or prevent GC.

Eukaryotic translation initiation factor EIF3H potentiates gastric carcinoma cell proliferation.

Eukaryotic translation initiation factor 3 subunit H (EIF3H) is required for the progression of several types of cancer. However, little is known about the function of EIF3H in gastric carcinoma. To address this issue, in the present study, we investigated EIF3H genetic alterations in and expression of EIF3H in gastric cancer tissue samples using cBioPortal and Oncomine databases. Endogenous EIF3H expression was knocked down in MGC80-3 and AGS gastric cancer cell lines by lentivirus-mediated RNA interference. We confirmed the knockdown efficiency by quantitative real-time PCR and western blotting and evaluated the effects of EIF3H silencing on cell proliferation of gastric cancer with the cell viability and colony formation assays and by flow cytometry. The OncoPrint of EIF3H generated using cBioPortal indicated that EIF3H genetic alterations (mutation, deletion and amplification) were present in two gastric cancer sample sets. The Oncomine analysis revealed that EIF3H mRNA level was upregulated in gastric cancer tissues. EIF3H knockdown inhibited cell proliferation and colony formation in gastric cancer lines and led to cell cycle arrest at the G0/G1 phase, while inducing apoptosis via up- and downregulation of pro- and anti-apoptotic factors, respectively. These results indicate that EIF3H can serve as a novel therapeutic target for the clinical treatment of gastric cancer.

Synergistic and low adverse effect cancer immunotherapy by immunogenic chemotherapy and locally expressed PD-L1 trap.

Although great success has been obtained in the clinic, the current immune checkpoint inhibitors still face two challenging problems: low response rate and immune-related adverse effects (irAEs). Here we report the combination of immunogenic chemotherapy and locally expressed PD-L1 trap fusion protein for efficacious and safe cancer immunotherapy. We demonstrate that oxaliplatin (OxP) boosts anti-PD-L1 mAb therapy against murine colorectal cancer. By design of a PD-L1 trap and loading its coding plasmid DNA into a lipid-protamine-DNA nanoparticle, PD-L1 trap is produced transiently and locally in the tumor microenvironment, and synergizes with OxP for tumor inhibition. Significantly, unlike the combination of OxP and anti-PD-L1 mAb, the combination of OxP and PD-L1 trap does not induce obvious Th17 cells accumulation in the spleen, indicating better tolerance and lower tendency to irAEs. The reports here may highlight the potential of applying PD-L1 inhibitor, especially locally expressed PD-L1 trap, in cancer therapy following OxP-based chemotherapy.

miR-148b inhibits glycolysis in gastric cancer through targeting SLC2A1.

Although the molecular biology of GC has been well characterized, early diagnostic biomarkers and effective therapeutic options in gastric cancer are still under investigation. Here, we found that miR-148b expression decreased in human gastric cancer tissues compared with matched adjacent nontumor tissues by q-PCR analysis and in situ hybridization. Further investigation revealed that overexpression of miR-148b limited glycolysis including glucose consumption, lactate production in gastric cancer cell lines BGC-823 and MKN45. Bioinformatics prediction uncovered that a dedicated transporters solute carrier family 2 member 1 (SLC2A1), also called GLUT1, was the direct target of miR-148b. The target effects were further confirmed by luciferase assay and western blot analysis. Besides, a reverse correlation was observed between relative SLC2A1 and miR-148b expression in human GC tissues compared with matched adjacent nontumor tissues. Subsequently, SLC2A1 suppression by SLC2A1 siRNA or specific inhibitor restricted the reduced effects of glycolysis mediated by miR-148b while SLC2A1 overexpression abrogated the effect of miR-148b on glycolysis. Our findings provided new evidence of miR-148b in GC development through restraining glycolysis, highlighting the role of miR-148b as a new target for GC treatment.