Clinical Correlation of Function and TCR vß Diversity of MAGE-C2-Specific CD8+ T Cell Response in Esophageal Cancer.

Melanoma-associated Ag (MAGE)-C2, an immunogenic cancer germline (testis) Ag, is highly expressed by various tumor cells, thymic medullary epithelial cells, and germ cells. In this study, we aimed to explore the immunologic properties of MAGE-C2-specific CD8+ T cells and the relationship of its TCR ß-chain V region (TCR vß) subfamily distribution to prognosis of patients with esophageal cancer. PBMCs and tumor-infiltrating lymphocytes expanded by CD3/CD28 Dynabeads and MAGE-C2 peptides in vitro resulted in the induction of lysosome-associated membrane protein-1 (LAMP-1 or CD107a) on the cell surface and the production of IFN-γ by MAGE-C2-specific CD8+ T cells. We found differential TCR vß subfamily distribution among flow-sorted CD107a+IFN-γ+ and CD107a-IFN-γ- CD8+ T cells. The proportion of CD107a+ and/or IFN-γ+ tetramer+ CD8+ T cells was lower in patients with lymph node metastasis, late tumor stage, and poorly differentiated state (p < 0.05). T-box transcription factor was positively correlated with CD107a and IFN-γ. Kaplan-Meier analysis showed that patients whose MAGE-C2-specific CD8+ T cells expressed high CD107a and/or IFN-γ had a longer survival time when compared with patients whose MAGE-C2-specific CD8+ T cells expressed low levels of CD107a and/or IFN-γ. Moreover, analysis of TCR vß subfamily distribution revealed that a higher frequency of TCR vß16 in MAGE-C2-specific CD8+ T cells was positively correlated with a better prognosis. These results suggest that the presence of functional MAGE-C2-specific CD8+ T cells had an independent prognostic impact on the survival of patients with esophageal cancer.

The association between dietary patterns before pregnancy and gestational diabetes mellitus: a matched case-control study in China.

BACKGROUND AND OBJECTIVES: We aimed to explore the relationship between dietary patterns and gestational diabetes mellitus (GDM) during pre-pregnancy six months using principal component analysis (PCA) and the geometric framework for nutrition (GFN). METHODS AND STUDY DESIGN: We conducted a case-control study that included 210 GDM pregnant women and 210 controls. The dietary intake of all participants was assessed by a validated semi-quantitative food frequency questionnaire (FFQ). Major dietary patterns were extracted by PCA. A conditional logistic regression model was used to determine whether specific dietary patterns are associated with the risk of GDM. Meanwhile, the relationship between dietary patterns and GDM was visualized using GFN. RESULTS: Four major dietary patterns were identified: "protein-rich pattern," "plant-based pattern," "oil-pickles-desserts pattern," and "cereals-nuts pattern." After adjustment for confounders, the "plant-based pattern" was associated with decreased risk of GDM (Q4 vs. Q1: OR = 0.01, 95% CI: 0.00-0.08), whereas no significant association was found in other dietary patterns. Moreover, there was no dietary intake of ice cream cones and deep-fried dough sticks for the population, which would produce fewer patients with GDM. Deep-fried dough sticks had statistically significant differences in the case and control groups (p < 0.001), while ice cream cones had the opposite result. CONCLUSIONS: The "plant-based pattern" may reduce the risk of GDM. Besides, although the "cereals-nuts pattern" had no association with GDM risk, avoiding the intake of deep-fried dough sticks could decrease GDM risk.

Nobiletin activates thermogenesis of brown and white adipose tissue in high-fat diet-fed C57BL/6 mice by shaping the gut microbiota.

Increasing energy expenditure by activating thermogenesis in brown and beige adipocytes is a critical approach to protect against obesity. Here, we investigated the action and mechanism of a natural polymethoxyflavone on adaptive thermogenesis in high-fat diet-induced obesity mouse model. Nobiletin treatment significantly ameliorated obesity, alleviated the whitening of brown adipose tissue, and promoted browning of white adipose tissue in mice fed a high-fat diet. Gut microbiota analysis and metabolomic profiling revealed that nobiletin treatment resulted in a composition shift in the gut microbiota thereby altering fermentation products acetate levels in the host feces and serum. Further, transplantation of the microbiota from nobiletin-treated mice to microbiota-depleted mice activated brown adipose tissue activity, promoted beige adipocytes formation, and improved high-fat diet-induced obesity. Our results indicate that nobiletin could be used as a dietary therapy to prevent HFD-induced obesity, and provide a potential target-specific gut microbial species-driven mechanism for activating thermogenesis in brown and beige adipocytes.

Dietary inflammatory index, inflammation biomarkers and preeclampsia risk: a hospital-based case-control study.

This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were -0·65 ± 1·58 for cases and -1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-ß) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-ß levels, were associated with increased preeclampsia risk.

Dietary and serum vitamin D and preeclampsia risk in Chinese pregnant women: a matched case-control study.

The effect of vitamin D (VD) on the risk of preeclampsia (PE) is uncertain. Few of previous studies focused on the relationship between dietary VD intake and PE risk. Therefore, we conducted this 1:1 matched case-control study to explore the association of dietary VD intake and serum VD concentrations with PE risk in Chinese pregnant women. A total of 440 pairs of participants were recruited during March 2016 to June 2019. Dietary information was obtained using a seventy-eight-item semi-quantitative FFQ. Serum concentrations of 25(OH)D2 and 25(OH)D3 were measured by liquid chromatography-tandem MS. Multivariate conditional logistic regression was used to estimate OR and 95 % CI. Restricted cubic splines (RCS) were plotted to evaluate the dose-response relationship of dietary VD intake and serum VD concentrations with PE risk. Compared with the lowest quartile, the OR of the highest quartile were 0·45 (95 % CI 0·29, 0·71, Ptrend = 0·001) for VD dietary intake and 0·26 (95 % CI 0·11, 0·60, Ptrend = 0·003) for serum levels after adjusting for confounders. In addition, the RCS analysis suggested a reverse J-shaped relationship between dietary VD intake and PE risk (P-nonlinearity = 0·02). A similar association was also found between serum concentrations of total 25(OH)D and PE risk (P-nonlinearity = 0·02). In conclusion, this study provides evidence that higher dietary intake and serum levels of VD are associated with the lower risk of PE in Chinese pregnant women.

Dietary patterns and sarcopenia in a Chinese population.

BACKGROUND AND OBJECTIVES: Malnutrition is implicated as a key modifiable risk factor for sarcopenia. As such, a dietary pattern analysis, rather than an analysis of single food items or nutrients, may provide insights into the comprehensive contribution of diet and nutrition to the risk of sarcopenia. Accordingly, the aim of this study was to evaluate the relationships between main dietary patterns and sarcopenia. METHODS AND STUDY DESIGN: A total of 591 participants aged over 40 years were included in this cross-sectional study. A validated food-frequency questionnaire was used to assess their dietary intake, and principal component analysis (PCA) was used to identify the main dietary patterns. A multivariate logistic regression model was used to explore the associations between their main dietary patterns and the risk of sarcopenia. RESULTS: This study identified 56 cases of sarcopenia, equating to an overall detection rate of 9.48%. The PCA revealed four major dietary patterns among the participants: "coarse cereals and vegetables"; "beverages and animal organs"; "poultry, fish and shrimp"; and "fruits and pasta". After adjusting for age, sex, physical activity and smoking, individuals with the "coarse cereals and vegetables" dietary pattern had a 63.0% reduction in the risk of sarcopenia. CONCLUSIONS: The "coarse cereals and vegetables" dietary pattern is negatively correlated with sarcopenia, and may reduce the risk of sarcopenia.

Sulforaphane activates CD8+ T cells antitumor response through IL-12RB2/MMP3/FasL-induced MDSCs apoptosis'.

BACKGROUND: Extensive attention has been given to the role of myeloid-derived suppressor cells (MDSCs) in driving tumor progression and treatment failure. Preclinical studies have identified multiple agents that eliminate MDSCs. However, none have been authorized in the cliniccal ues due to the safety reasons. In the present study, we investigated the efficacy and mechanism of sulforaphane (SFN) to eliminate MDSCs in the tumor microenvironment (TME). METHODS: We monitored SFN effect on tumor growth and the percents or apoptosis of immune cell subsets in mice models bearing LLC or B16 cells. Flow cytometry, quantitative reverse transcription-PCR, immunohistochemistry, ELISA, immunofluorescence, imaging flow cytometry and western blot were performed to validate the role of SFN on MDSCs function in vivo and in vitro. RNA sequencing was then used to interrogate the mechanisms of how SFN regulated MDSCs function. Tumor xenograft models were established to evaluate the involvement of IL-12RB2/MMP3/FasL induced MDSCs apoptosis in vivo. We verified the effect of SFN on MDSCs and CD8+ T cells in the blood samples from a phase I clinical trial (KY-2021-0350). RESULTS: In this study, we elucidated that SFN liberated CD8+ T-cell antitumor ability by reducing MDSCs abundance, leading to repressed tumor growth. SFN treatment suppressed MDSCs accumulation in the peripheral blood and tumor sites of mice, but had no effect on the bone marrow. Mechanistically, SFN activates IL-12RB2, which stimulates the MMP3/FasL signaling cascade to trigger caspase 3 cleavage and induce apoptosis in MDSCs. Clinically, SFN treatment eliminates peripheral MDSCs and increases the percentage and activation of CD8+ T cells. CONCLUSIONS: Collectively, we uncovered the role of SFN in eliminating MDSCs to emancipate CD8+ T cells through IL-12RB2/MMP3/FasL induced apoptosis, thus providing a strategy for targeting MDSCs to control tumors and improve clinical efficacy.

Association between ultra-processed foods and risk of cancer: a systematic review and meta-analysis.

Background: Despite increasing evidence that has shown the association of ultra-processed foods (UPFs) with cancer risk, the results remain inconclusive. We, therefore, conducted the meta-analysis to clarify the association by including recently published studies. Methods: A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies from inception to January 2023. To pool data, fixed-effects or random-effects models were used where appropriate. Subgroup analyses, sensitivity analyses, and publication bias tests were performed. Results: A total of 13 studies (4 cohort studies and 9 case-control studies) were included in the analysis, with a total of 625,738 participants. The highest UPFs consumption was associated with increased risk of colorectal cancer (OR = 1.23, 95% CI: 1.10-1.38), colon cancer (OR = 1.25, 95% CI: 1.14-1.36), and breast cancer (OR = 1.10, 95% CI: 1.00-1.20) but not rectal cancer (OR = 1.18, 95% CI: 0.97-1.43) and prostate cancer (OR = 1.03, 95% CI: 0.93-1.12). In addition, the subgroup analyses showed that a positive association between UPFs consumption and colorectal cancer was observed among men (OR = 1.31, 95% CI: 1.15-1.50), whereas no significant association was observed among women (OR = 1.10, 95% CI: 0.94-1.29). Conclusion: The present meta-analysis suggests that high UPFs consumption is associated with a significantly increased risk of certain site-specific cancers, especially the digestive tract and some hormone-related cancers. However, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Effect of ginger in the treatment of nausea and vomiting compared with vitamin B6 and placebo during pregnancy: a meta-analysis.

INTRODUCTION: Nausea and vomiting (NV) affect up to 85% of pregnant women, which has multiple effects on pregnancy outcome. The truth etiology of nausea and vomiting in pregnancy (NVP) is still unknown. Considering the potential teratogenic effect in fetus due to chemical drugs, ginger can be used to treat nausea and vomiting during pregnancy. Reports have shown that ginger can reduce the severity of NV, however, these results are controversial. Therefore, this meta-analysis aims to explore the effect of ginger in the treatment of nausea and vomiting during pregnancy compared with placebo and vitamin B6. METHODS: The randomized control trials (RCTs) on the association with ginger and pregnancy-related nausea and vomiting were searched and identified in two databases Web of Science and PubMed (up to April 2019). Stata software was used to conduct meta-analysis. In addition, the source of heterogeneity explored by metaregression, sensitivity analysis, subgroup analyses, the publication bias were assessed by Egger's tests and Funnel plot, p < .05 was considered to be significant. RESULTS: Thirteen studies involving 1174 subjects were included in this meta-analysis. The result demonstrated that ginger intervention has significant effect in improving general symptom of NVP [OR = 7.475, 95% CI = (4.133, 13.520), I2 = 30.1%], relieving severity of nausea [SMD = 0.821, 95% CI = (0.585, 1.056), I2 = 38.9%], but not significant in reducing vomiting [SMD = 0.549, 95% CI = (-0.268, 1.365), I2 = 91.4%], compared with placebo. Besides, ginger intervention has no significant effect on improving general symptom of NVP [OR = 1.239, 95% CI = (0.495, 3.102), I2 = 57.3%], relieving severity of nausea [SMD = 0.199, 95% CI = (-0.102, 0.500), I2 = 65.7%], reducing vomiting [SMD = 0.331, 95% CI = (-0.145, 0.808), I2 = 85.9%], compared with vitamin B6. CONCLUSIONS: Ginger supplementation significantly relieve general NVP symptom and nausea compared with placebo, but no significant effect on vomiting. Moreover, ginger is more effective than vitamin B6 in treating NVP, although, there were no significant differences. Further, rigidly designed RCTs with larger sample sizes are needed to verify the effectiveness of ginger supplementation for treatment NVP compared with vitamin B6.

Adherence to a Dietary Approaches to Stop Hypertension (DASH)-style Diet in Relation to Preeclampsia: A Case-Control Study.

Maternal diet is an important potential factor associated with the risk of preeclampsia. However, it is unclear whether adherence to a Dietary Approaches to Stop Hypertension (DASH)-style diet can reduce the development of preeclampsia. To examine the potential association, we conducted a hospital-based case-control study at the First Affiliated Hospital of Zhengzhou University, China. A total of 449 cases with preeclampsia and 449 controls were studied. Dietary information was collected using a validated food frequency questionnaire (FFQ). DASH scores were calculated according to nutrients/food emphasised or minimised in the DASH diet. The calculated DASH scores ranged from 11 to 38 for all of the participants, and the DASH scores of the cases were significantly lower than those of the controls (23.48 ± 4.58 vs 24.51 ± 4.51; p = 0.001). Participants in the fourth quartile of the DASH score were 45% less likely to have preeclampsia than those in the first quartile in the crude model (Q4 vs Q1, odds ratio [OR]: 0.55; 95% confidence interval [CI]: 0.38, 0.80; ptrend = 0.001). The relationship remained significant in the model adjusted for multiple confounders, especially for major risk factors of preeclampsia (OR: 0.53; 95% CI: 0.36, 0.78; ptrend = 0.001). Our findings suggest an inverse relationship between adherence to a DASH-style diet and the odds of preeclampsia. Further larger-scale cohort studies or randomised controlled trials are warranted to confirm these relationships.

Effect of whole-course nutrition management on patients with esophageal cancer undergoing concurrent chemoradiotherapy: A randomized control trial.

OBJECTIVES: Malnutrition is the most common complication of patients with esophageal cancer and can lead to poor prognosis and death. Good nutritional status has been shown to help improve patient outcomes and reduce complications. In the absence of specific evidence on the effect of nutrition in patients with esophageal cancer, the purpose of this study was to investigate the effect of whole-course nutrition management on the prognosis and complications of chemoradiotherapy in patients with esophageal cancer through a randomized controlled trial. METHODS: A total of 96 patients with esophageal cancer treated with concurrent chemoradiation were randomized to an intervention group (treated with whole-course nutrition management from the Nutrition Support Team) and a control group (treated with the general nutritional method) for approximately 6 wk. Dietary surveys and body measurements were conducted at baseline and every day thereafter. Patient-generated Subjective Global Assessment score, blood index, quality of life, and psychological condition were assessed at baseline and every week before discharge. Complications (e.g., radiation esophagitis, myelosuppression, and skin symptoms), completion rates of therapy, short-term efficacy evaluation, as well as clinical outcomes were measured. RESULTS: A total of 85 patients completed the study (intervention group = 45; control group = 40). There were significant differences in the changes of serum albumin and total protein between the two groups throughout the trial (P < 0.05). Complications (e.g., radioactive esophagitis, skin symptom of complications) and quality of life were statistically different before and after the intervention (P < 0.05). The difference in the change of other indicators was not statistically significant. CONCLUSIONS: Whole-course nutrition management can improve the nutritional status of patients with esophageal cancer treated with concurrent chemoradiotherapy, reduce the severity of radiation esophagitis and radiation skin reactions, improve the quality of life, and relieve depressive symptoms.

The role of the triglyceride (triacylglycerol) glucose index in the development of cardiovascular events: a retrospective cohort analysis.

This study aimed to evaluate the role of the triglyceride (triacylglycerol) glucose (TyG) index in predicting and mediating the development of cardiovascular disease (CVD). This cohort study included 6078 participants aged over 60 years who participated in a routine health check-up programme from 2011 to 2017. The competing risk model, cox regression model and multimediator analyses were performed. TyG was calculated as ln [fasting triglyceride (mg/dl) × fasting plasma glucose (mg/dl)/2]. During a median 6 years of follow-up, 705 (21.01/1000 person-years) CVD events occurred. In fully adjusted analyses, quartiles 3 and 4 versus quartile 1 of TyG index (adjusted subhazard ratios [SHRs] 1.33 [95% CI: 1.05-1.68] and 1.72 [1.37-2.16]) were associated with an increased risk of CVD events. The continuous time-dependent TyG remained significant in predicting CVD events (adjusted hazard ratios [HR] 1.43 [1.24-1.63]). The adverse estimated effects of body mass index (BMI) or resting heart rate (RHR) on CVD mediated through the joint effect of the baseline and follow-up TyG index. In addition, an effect mediated only through the follow-up TyG existed (P < 0.05). Thus, it is necessary to routinely measure the TyG. The TyG index might be useful for predicting CVD events in clinical practice.

Hospital use in survivors of transient ischaemic attack compared with survivors of stroke in central China: a nested case-control study.

OBJECTIVES: There is a lack of knowledge regarding post-discharge hospitalisation utilisation after transient ischaemic attack (TIA) in China. The aim of this study is to quantify rehospitalisation use in survivors of TIA compared with their own previous hospital use and matched survivors of stroke. DESIGN: Nested case-control study of electronic medical records datasets. SETTING: 958 hospitals in Henan, China, from July 2012 to December 2015. PARTICIPANTS: In total, 4823 survivors of stroke were matched to the TIA cohort (average age: 64.5 years; proportion of men: 48.4%) at a 1:1 ratio. All subjects with an onset of stroke/TIA were recorded with a 1-year look-back and follow-up. OUTCOME MEASURES: Adjusted difference-in-differences (DID) values in 1-year hospital lengths of stay (LOSs) and readmission within 7, 30 and 90 days. RESULTS: There was an increase in hospital admissions in survivors of TIA in the year after the index hospitalisation compared with the prior year. Of the 2449 rehospitalisation events that occurred during the first year after TIA, stroke (20.6%) was the most common reason for rehospitalisation. There was no difference in the stroke-specific readmission rates between the TIA and stroke cohorts (p=0.198). The TIA cohort had fewer readmissions within 30 days and 90 days after all-cause discharge compared with the controls. The corresponding covariate-adjusted DID values were -3.5 percentage points (95% CI -5.3 to -1.8) and -4.5 (95% CI -6.5 to -2.4), respectively. A similar trend was observed in the 1-year LOS. In the stratified analysis, the DID reductions were not significant in patients with more comorbidities or in rural patients. CONCLUSIONS: Compared with survivors of stroke, survivors of TIA use fewer hospital resources up to 1 year post-discharge. Greater attention to TIAs among patients with more comorbidities and rural patients may provide an opportunity to reduce hospital use.