Ultra-processed food consumption and the risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1 :1.49; 95% confidence interval [CI]: 1.07-2.07; Ptrend  = .021) in a linear dose-response manner (Pnonlinearity  = .075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1 :2.17; 95% CI: 1.14-4.15) than in those aged ≥65 years (HRquartile 4 vs 1 :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (Pinteraction  = .061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence.

Type 2 Diabetes-Prevention Diet and All-Cause and Cause-Specific Mortality: A Prospective Study.

We aimed to examine whether type 2 diabetes-prevention diet, a dietary pattern previously developed for reducing type 2 diabetes risk, was associated with mortality in a US population. A population-based cohort of 86,633 subjects was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2015). Dietary information was collected with a food frequency questionnaire. A dietary diabetes risk-reduction score was calculated to reflect adherence to this dietary pattern, with higher scores representing better adherence. Hazard ratios (HRs) and absolute risk differences (ARDs) in mortality rates per 10,000 person-years were calculated. After a mean follow-up of 13.6 years, 17,532 all-cause deaths were observed. Participants with the highest versus the lowest quintiles of dietary diabetes risk-reduction score were observed to have decreased risks of death from all causes (HR = 0.76, 95% CI: 0.72, 0.80; ARD: -81.94, 95% CI: -93.76, -71.12), cardiovascular disease (HR = 0.73, 95% CI: 0.66, 0.81; ARD: -17.82, 95% CI: -24.81, -11.30), and cancer (HR = 0.85, 95% CI: 0.78, 0.94; ARD: -9.92, 95% CI: -15.86, -3.59), which were modified by sex, smoking status, or alcohol consumption in subgroup analyses (P for interaction < 0.05 for all). In conclusion, a type 2 diabetes-prevention diet confers reduced risks of death from all causes, cardiovascular disease, and cancer in this US population.

Frailty and risks of all-cause and cause-specific death in community-dwelling adults: a systematic review and meta-analysis.

BACKGROUND: The associations of frailty with all-cause and cause-specific mortality remain unclear. Therefore, we performed this meta-analysis to fill this gap. METHODS: We searched the PubMed and Embase databases through June 2022. Prospective cohort studies or clinical trials examining frailty were evaluated, and the multiple adjusted risk estimates of all-cause and cause-specific mortality, such as death from cardiovascular disease (CVD), cancer, respiratory illness, dementia, infection, and coronavirus disease 2019 (COVID-19), were included. A random effects model was used to calculate the summary hazard ratio (HR). RESULTS: Fifty-eight studies were included for the qualitative systematic review, of which fifty-six studies were eligible for the quantitative meta-analysis, and the studies included a total of 1,852,951 individuals and more than 145,276 deaths. Compared with healthy adults, frail adults had a significantly higher risk of mortality from all causes (HR 2.40; 95% CI 2.17-2.65), CVD (HR 2.64; 95% CI 2.20-3.17), respiratory illness (HR 4.91; 95% CI 2.97-8.12), and cancer (HR 1.97; 95% CI 1.50-2.57). Similar results were found for the association between prefrail adults and mortality risk. In addition, based on the studies that have reported the HRs of the mortality risk per 0.1 and per 0.01 increase in the frailty index, we obtained consistent results. CONCLUSIONS: The present study demonstrated that frailty was not only significantly related to an increased risk of all-cause mortality but was also a strong predictor of cause-specific mortality from CVD, cancer, and respiratory illness in community-dwelling adults. More studies are warranted to clarify the relationship between frailty and cause-specific mortality from dementia, infection, and COVID-19. TRIAL REGISTRATION: PROSPERO (CRD42021276021).

Low-carbohydrate diets and the risk of pancreatic cancer: a large prospective cohort study.

Low-carbohydrate diets have become a popular approach for weight loss in recent years. However, whether low-carbohydrate diets are associated with the risk of pancreatic cancer remains to be elucidated. Hence, we examined the association of low-carbohydrate diets with the risk of pancreatic cancer in a US population. A population-based cohort of 95 962 individuals was identified. A low-carbohydrate-diet score was calculated to quantify adherence to this dietary pattern, with higher scores indicating greater adherence. Cox regression was used to calculate risk estimate for the association of the low-carbohydrate-diet score with the risk of pancreatic cancer. Subgroup analysis was used to identify the potential effect modifiers. After an average follow-up of 8.87 years (875856.9 person-years), we documented a total of 351 pancreatic cancer cases. In the fully adjusted model, the highest versus the lowest quartiles of the overall low-carbohydrate-diet score were found to be associated with a reduced risk of pancreatic cancer (hazard ratioquartile 4 versus 1: 0.61; 95% confidence interval: 0.45, 0.82; Ptrend < 0.001). Subgroup analysis found that the inverse association of low-carbohydrate diets with the risk of pancreatic cancer was more pronounced in individuals aged ≥65 years than in those aged <65 years (Pinteraction = 0.015). Similar results were obtained for animal and vegetable low-carbohydrate-diet scores. In conclusion, low-carbohydrate diets, regardless of the type of protein and fat, are associated with a lower risk of pancreatic cancer in the US population, suggesting that adherence to low-carbohydrate diets may be beneficial for pancreatic cancer prevention. Future studies should validate our findings in other populations.

Dietary Vitamin K Intake and the Risk of Pancreatic Cancer: A Prospective Study of 101,695 American Adults.

No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose-response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.

Association of ultra-processed food consumption with cardiovascular mortality in the US population: long-term results from a large prospective multicenter study.

BACKGROUND: Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population. METHODS: A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers. RESULTS: After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36-1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50-1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76-1.17). A nonlinear dose-response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (all Pinteraction < 0.05). CONCLUSIONS: High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.

Dietary inflammatory index and incidence of and death from primary liver cancer: A prospective study of 103,902 American adults.

Chronic inflammation plays an important role in primary liver cancer (PLC) etiology and can be influenced by dietary habits. No prospective study has investigated the association of dietary inflammatory index (DII) with PLC incidence and mortality. Therefore, we used prospective data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to fill this gap. The DII was calculated from a validated 137-item food frequency questionnaire in a cohort of 103,902 individuals. Cox regression was used to estimate hazard ratios (HRs) for PLC incidence, and competing risk regression was used to estimate subdistribution HRs (SHRs) for PLC mortality. Restricted cubic spline regression was employed to identify the potential dose-response pattern. A total of 120 PLC cases and 102 PLC deaths were observed during follow-up. Higher DII scores from food and supplement were found to be associated with higher risks of developing PLC (HRTertile 3 vs. 1 2.05; 95% confidence interval [CI] 1.23-3.41) and death from this disease (SHRTertile 3 vs. 1 1.97; 95% CI 1.13-3.41). Similar results were obtained for DII score from food only. A nonlinear dose-response pattern was identified for the aforementioned associations (all pnonlinearity < 0.05). Overall, a more pro-inflammatory diet, as suggested by higher DII scores, is associated with higher risks of PLC incidence and mortality. These findings indicate that encouraging intake of more anti-inflammatory dietary components and reducing intake of pro-inflammatory components represent an attractive strategy to reduce PLC incidence and mortality.

Magnesium intake and primary liver cancer incidence and mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs. 1 : 0.44; 95% confidence interval: 0.24, 0.80; ptrend = 0.0065) and mortality (subdistribution hazard ratiotertile 3 vs. 1 : 0.37; 95% confidence interval: 0.19, 0.71; ptrend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose-response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all pnonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose-response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.

Efficacy and cost-effectiveness of fecal immunochemical test versus colonoscopy in colorectal cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The fecal immunochemical test (FIT) and colonoscopy are the most commonly used strategies for colorectal cancer (CRC) screening worldwide. We aimed to compare their efficacy and cost-effectiveness in CRC screening in an average-risk population. METHODS: PubMed, Embase, and National Health Services Economic Evaluation Database were searched. Risk ratio (RR) was used to evaluate the differences in detection rates of colorectal neoplasia between FIT and colonoscopy groups. A random-effects model was used to pool RRs. Incremental cost-effectiveness ratios (ICERs) were calculated to evaluate the cost-effectiveness of FIT versus colonoscopy. RESULTS: Six randomized controlled trials and 17 cost-effectiveness studies were included. The participation rate in the FIT group was higher than that in the colonoscopy group (41.6% vs 21.9%). In the intention-to-treat analysis, FIT had a detection rate of CRC comparable with colonoscopy (RR, .73; 95% confidence interval, .37-1.42) and lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Most included cost-effectiveness studies showed that annual (13/15) or biennial (5/6) FIT was cost-saving (ICER < $0) or very cost-effective ($0 < ICER ≤ $25000/quality-adjusted life-year) compared with colonoscopy every 10 years. CONCLUSIONS: FIT may be similar to 1-time colonoscopy in the detection rate of CRC, although it has lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Furthermore, annual or biennial FIT appears to be very cost-effective or cost-saving compared with colonoscopy every 10 years. These findings indicate, at least partly, that FIT is noninferior to colonoscopy in CRC screening in an average-risk population. Our findings should be treated with caution and need to be further confirmed.

Chronic obstructive pulmonary disease, lung function and risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies.

BACKGROUND: The association between chronic obstructive pulmonary disease (COPD), lung function and risk of type 2 diabetes mellitus (T2DM) remains controversial. We performed a meta-analysis to clarify this issue. METHODS: The PubMed and EMBASE databases were searched. Cohort studies on COPD, lung function and risk of T2DM in adults were included. A random effects model was adopted to calculate the summary risk ratio (RR) and 95% confidence interval (CI). Dose-response analysis was conducted where possible. RESULTS: A total of 13 eligible cohort studies involving 307,335 incident T2DM cases and 7,683,784 individuals were included. The risk of T2DM was significantly higher in patients with COPD than those without COPD (RR = 1.25, 95% CI 1.16-1.34). Compared to the highest category of percentage forced vital capacity (FVC%), the lowest category of FVC% was associated with a higher risk of T2DM (RR = 1.43, 95% CI 1.33-1.53). Similarly, the summary RR of T2DM for the lowest versus highest category of percentage forced expiratory volume in 1 s (FEV1%) was 1.49 (95% CI 1.39-1.60). Significant linear associations of FVC% and FEV1% with risk of T2DM were found (Pnon-linearity > 0.05); the RR of T2DM was 0.88 (95% CI 0.82-0.95) and 0.87 (95% CI 0.81-0.94) per 10% increase in FVC% and FEV1%, respectively. There was a non-significant relationship between the FEV1/FVC ratio and the risk of T2DM. CONCLUSIONS: Both COPD and impaired lung function, especially restricted ventilation dysfunction, could increase the risk of T2DM. However, these findings should be interpreted with caution due to the limited number of studies, and need to be validated by future studies.

Profiles of HBcrAg and pgRNA in Pregnant Women With Chronic HBV Under Different Disease Phases and Antiviral Prophylaxis.

Background: Pregnant women with chronic hepatitis B (CHB) exhibit unique clinical features in terms of postpartum immune system reconstitution and recovery from pregnancy-related changes. However, current studies focus primarily on the outcomes of maternal-infant transmission and postpartum hepatitis flares. We aimed to evaluate the profiles of hepatitis B core-related antigen (HBcrAg) and pregenomic RNA (pgRNA) in pregnant women with CHB. Methods: This retrospective analysis included treatment-naïve pregnant women with CHB who were followed up regularly in an outpatient clinic from 2014 to 2021. Baseline HBcrAg and pgRNA levels were compared in patients with different disease phases. Changes in these parameters were examined in a subset of patients receiving antiviral prophylaxis. HBcrAg and pgRNA levels were measured before treatment, at 32 weeks of gestation, and postpartum. Results: The final analysis included a total of 121 patients, 100 of whom were hepatitis B e antigen (HBeAg)-positive (96 and 4 in the immune-tolerant and -indeterminate phases, respectively) and 21 of whom were HBeAg-negative (6 and 15 in the immune-active and -inactive carrier phases, respectively). The HBeAg-negative group vs the HBeAg-positive group had lower levels of baseline HBcrAg (median [interquartile range {IQR}], 3.7 [3.0-5.9] vs 8.6 [8.4-8.7] log10 U/mL; P < .01) and pgRNA (median [IQR], 0.0 [0.0-2.5] vs 7.8 [7.6-8.1] log10 copies/mL; P < .01). The serum levels of HBcrAg and pgRNA were highest in immune-tolerant carriers and lowest in immune-inactive carriers. In HBeAg-positive patients, the correlation coefficients of HBcrAg and pgRNA with hepatitis B virus (HBV) DNA were 0.40 and 0.43, respectively; in HBeAg-negative patients, they were 0.53 and 0.51, respectively (all P < .05). The correlation coefficients with hepatitis B surface antigen (HBsAg) were 0.55 and 0.52 (P < .05) in HBeAg-positive patients, respectively, while in HBeAg-negative patients they were 0.42 and 0.37, respectively (P > .05). Among 96 patients receiving antiviral prophylaxis, we detected a rapid decrease in HBV DNA to an undetectable level during treatment but relatively stable levels of pgRNA and HBcrAg. Conclusions: HBcrAg and pgRNA levels are lower in HBeAg-negative patients than in HBeAg-positive patients. These 2 markers are significantly associated with HBV DNA irrespective of HBeAg status, while they are significantly associated with HBsAg only in HBeAg-positive patients.

m6A demethylation of FOSL1 mRNA protects hepatoma cells against necrosis under glucose deprivation.

Stress-adaptive mechanisms enabling cancer cells to survive under glucose deprivation remain elusive. N6-methyladenosine (m6A) modification plays important roles in determining cancer cell fate and cellular stress response to nutrient deficiency. However, whether m6A modification functions in the regulation of cancer cell survival under glucose deprivation is unknown. Here, we found that glucose deprivation reduced m6A modification levels. Increasing m6A modification resulted in increased hepatoma cell necrosis under glucose deprivation, whereas decreasing m6A modification had an opposite effect. Integrated m6A-seq and RNA-seq revealed potential targets of m6A modification under glucose deprivation, including the transcription factor FOSL1; further, glucose deprivation upregulated FOSL1 by inhibiting FOSL1 mRNA decay in an m6A-YTHDF2-dependent manner through reducing m6A modification in its exon1 and 5'-UTR regions. Functionally, FOSL1 protected hepatoma cells against glucose deprivation-induced necrosis in vitro and in vivo. Mechanistically, FOSL1 transcriptionally repressed ATF3 by binding to its promoter. Meanwhile, ATF3 and MAFF interacted via their leucine zipper domains to form a heterodimer, which competed with NRF2 for binding to antioxidant response elements in the promoters of NRF2 target genes, thereby inhibiting their transcription. Consequently, FOSL1 reduced the formation of the ATF3-MAFF heterodimer, thereby enhancing NRF2 transcriptional activity and the antioxidant capacity of glucose-deprived-hepatoma cells. Thus, FOSL1 alleviated the necrosis-inducing effect of glucose deprivation-induced reactive oxygen species accumulation. Collectively, our study uncovers the protective role of m6A-FOSL1-ATF3 axis in hepatoma cell necrosis under glucose deprivation, and may provide new targets for cancer therapy.

Plant-based diets and the risk of pancreatic cancer: a large prospective multicenter study.

BACKGROUND: Plant-based diets have been recommended for improving health outcomes, including cancer. However, previous studies on plant-based diets and the risk of pancreatic cancer are scarce and fail to consider plant food quality. OBJECTIVES: We sought to examine the potential associations of 3 plant-based diet indices (PDIs) with the risk of pancreatic cancer in a US population. METHODS: A population-based cohort of 101,748 US adults was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The overall PDI, healthful PDI (hPDI), and unhealthful PDI (uPDI) were constructed to qualify adherence to overall, healthy, and less healthy plant-based diets, respectively, with higher scores indicating better adherence. Multivariable Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was conducted to identify the potential effect modifiers. RESULTS: Over a mean follow-up of 8.86 years, 421 pancreatic cancer cases occurred. Participants in the highest compared with the lowest quartiles of overall PDI had a lower risk of pancreatic cancer [HRquartile 4 versus 1: 0.74; 95% confidence interval (CI): 0.57, 0.96; Ptrend = 0.023]. A stronger inverse association was observed for hPDI (HRquartile 4 versus 1: 0.56; 95% CI: 0.42, 0.75; Ptrend < 0.001). Conversely, uPDI was positively associated with the risk of pancreatic cancer (HRquartile 4 versus 1: 1.38; 95% CI: 1.02, 1.85; Ptrend = 0.012). Subgroup analyses revealed a stronger positive association for uPDI in participants with BMI <25 (HRquartile 4 versus 1: 3.22; 95% CI: 1.56, 6.65) than in those with BMI ≥25 (HRquartile 4 versus 1: 1.08; 95% CI: 0.78, 1.51) (Pinteraction = 0.001). CONCLUSIONS: In this US population, adherence to a healthy plant-based diet confers a lower risk of pancreatic cancer, whereas adherence to a less healthy plant-based diet confers a higher risk. These findings highlight the importance of considering plant food quality in preventing pancreatic cancer.

Integrative analysis reveals that SLC38A1 promotes hepatocellular carcinoma development via PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism.

Although hepatocellular carcinoma (HCC) is rather frequent, little is known about the molecular pathways underlying its development, progression, and prognosis. In the current study, we comprehensively analyzed the deferentially expressed metabolism-related genes (MRGs) in HCC based on TCGA datasets attempting to discover the potentially prognostic genes in HCC. The up-regulated MRGs were further subjected to analyze their prognostic values and protein expressions. Twenty-seven genes were identified because their high expressions were significant in OS, PFS, DFS, DSS, and HCC tumor samples. They were then used for GO, KEGG, methylation, genetics changes, immune infiltration analyses. Moreover, we established a prognostic model in HCC using univariate assays and LASSO regression based on these MRGs. Additionally, we also found that SLC38A1, an amino acid metabolism closely related transporter, was a potential prognostic gene in HCC, and its function in HCC was further studied using experiments. We found that the knockdown of SLC38A1 notably suppressed the growth and migration of HCC cells. Further studies revealed that SLC38A1 modulated the development of HCC cells by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism. In conclusion, this study identified the potentially prognostic MRGs in HCC and uncovered that SLC38A1 regulated HCC development and progression by regulating PI3K/AKT/mTOR signaling via glutamine mediated energy metabolism, which might provide a novel marker and potential therapeutic target in HCC.

Prediagnosis ultra-processed food consumption and prognosis of patients with colorectal, lung, prostate, or breast cancer: a large prospective multicenter study.

Background and aims: Whether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer. Methods: This study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality. Results: High ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose-response manner (all Pnonlinearity < 0.05), whereas no significant results were found for other associations of interest. Subgroup analyses additionally revealed a significantly positive association with colorectal cancer-specific mortality among colorectal cancer patients in stages I and II but not among those in stages III and IV (Pinteraction = 0.006), and with prostate cancer-specific mortality among prostate cancer patients with body mass index <25 but not among those with body mass index ≥25 (Pinteraction = 0.001). Conclusion: Our study suggests that reducing ultra-processed food consumption before cancer diagnosis may improve the overall survival of patients with lung or prostate cancer, and the cancer-specific survival of certain subgroups of patients with colorectal or prostate cancer.

Egg consumption and risks of all-cause and cause-specific mortality: a dose-response meta-analysis of prospective cohort studies.

CONTEXT: Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the dose-response association of egg consumption with risk of mortality has not been determined. OBJECTIVE: To determine the potential dose-response association of egg consumption with risk of mortality in the general population. DATA SOURCES: The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021. DATA EXTRACTION: Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system. DATA ANALYSIS: Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01-1.15) for all-cause mortality, 1.07 (95%CI, 0.97-1.18) for cardiovascular disease-caused mortality, and 1.16 (95%CI, 1.04-1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease-caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011). CONCLUSIONS: Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.

Fried food consumption and the risk of pancreatic cancer: A large prospective multicenter study.

Background and aims: Whether fried food consumption is associated with the risk of pancreatic cancer remains elusive. We aimed to examine this association in a US population. Methods: A population-based cohort of 101,729 US adults was identified. Fried food consumption was assessed with a validated food frequency questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. Explanatory analyses were conducted to identify main contributor(s) to the observed association. Results: During an average follow-up of 8.86 years (900871.2 person-years), 402 pancreatic cancer cases occurred. High consumption of total fried foods (deep-fried plus pan-fried foods; HRquartile4 vs. 1 0.71, 95% CI 0.51-0.99, P trend = 0.047) and deep-fried foods (HRquartile 4 vs. 1 0.64, 95% CI 0.47-0.88, P trend = 0.011), but not pan-fried foods (HRquartile 4 vs. 1 0.98, 95% CI 0.73-1.32; P trend = 0.815), was found to be associated with a reduced risk of pancreatic cancer in a non-linear dose-response manner, which was not modified by predefined stratification factors and persisted in sensitivity analyses. In explanatory analyses, only chip consumption was found to be inversely associated with the risk of pancreatic cancer; consistently, the initial significant associations between total fried food and deep-fried food consumption and the risk of pancreatic cancer changed to be non-significant after omitting or further adjusting for chip consumption. Conclusion: Consumption of deep-fried foods, but not pan-fried foods, is inversely associated with the risk of pancreatic cancer in this US population. The role of deep-fried foods in reducing the risk of pancreatic cancer appears to be mainly attributable to chips. More studies are needed to confirm our findings in other populations and settings.

PgRNA kinetics predict HBsAg reduction in pregnant chronic hepatitis B carriers after treatment cessation.

Background: Pregenomic RNA (pgRNA) and hepatitis B core-related antigen (HBcrAg) play significant roles in predicting discontinuing treatment outcomes. However, their role in pregnancy has rarely been reported. We aimed to evaluate the performance of pgRNA and HBcrAg kinetics in predicting HBeAg seroconversion and HBsAg reduction postpartum in HBeAg-positive pregnant women. Methods: Pregnant HBeAg-positive patients receiving antiviral prophylaxis and ceasing treatment postpartum were included. PgRNA and HBcrAg levels were measured before treatment, at 32 weeks of gestation, and at treatment withdrawal postpartum. Other virological and biochemical parameters were regularly examined until 96 weeks postpartum. Results: Of 76 pregnant chronic hepatitis B (CHB) carriers with a median treatment duration of 18.1 weeks, HBeAg seroconversion and HBsAg reduction >0.3 log10 IU/mL at 96 weeks postpartum occurred in 8 (10.5%) and 13 (17.1%) patients, respectively. HBsAg correlated most strongly with pgRNA, while HBeAg correlated most strongly with HBcrAg. Multivariable regression analysis revealed that postpartum pgRNA decline and peak ALT levels were independent predictors of HBsAg reduction. The area under the curve of the regression model was 0.79 and reached as high as 0.76 through bootstrapping validation. The calibration plot showed that the nomogram had a performance similar to that of the ideal model. A decision tree was established to facilitate application of the nomogram. In addition, HBcrAg kinetics, as an independent predictor, performed poorly in predicting HBeAg seroconversion. Conclusions: Postpartum pgRNA decline together with peak ALT levels may identify patients with a higher probability of HBsAg reduction after treatment cessation postpartum among pregnant CHB carriers receiving antiviral prophylaxis.

A Nomogram for Predicting Non-Rebound in HBV-Infected Pregnant Women With Mother-to-Child Transmission Prevention.

Background: Current guidelines recommend that pregnancies with mother-to-child transmission (MTCT) prevention can cease antiviral treatment after delivery. We aimed to develop a nomogram for predicting non-rebound in HBV-infected pregnant women with MTCT prevention after post-partum nucleos(t)ide analogs (NAs) withdrawal based on parameters before treatment cessation. Methods: Pregnant women receiving antiviral therapy for MTCT prevention and who withdrew from taking NAs after delivery were included in this study. We used the least absolute shrinkage and selection operator (LASSO) logistics and a two-way stepwise regression to select prognostic factors for the risk model, and the concordance index (C-index) was used to assess its discrimination. Internal validation was performed through bootstrapping. Results: Of 92 included patients, 16 and 76 experienced non-rebound and virologic rebound within 48 weeks of post-partum NAs cessation, respectively. Platelet to lymphocyte ratio (PLR) at 34 ± 2 weeks of gestation, a reduction in hepatitis B surface antigen (HBsAg) from baseline to 34 ± 2 weeks of gestation, and hepatitis B virus (HBV) DNA declining from baseline to the end of treatment (EOT) were entered into the final risk model. Its C-index was 0.91 (95% CI, 0.82-0.99), and it reached as high as 0.88 after bootstrapping validation. The decision curve and decision tree were further developed to facilitate the application of this model. Conclusions: We developed a nomogram for predicting non-rebound in pregnant women with MTCT prevention after the withdrawal of antiviral agents, which facilitates physicians in making appropriate treatment recommendations.

Suppression of Heterogeneous Nuclear Ribonucleoprotein C Inhibit Hepatocellular Carcinoma Proliferation, Migration, and Invasion via Ras/MAPK Signaling Pathway.

Hepatocellular carcinoma (HCC), the most common malignant tumor, has high fatality and recurrence rates. Accumulating evidence shows that heterogeneous nuclear ribonucleoprotein C (HNRNPC), which is mainly involved in RNA splicing, export, and translation, promotes progression and metastasis of multiple tumor types; however, the effects of HNRNPC in HCC are unknown. In the present study, high levels of HNRNPC were detected in tumor tissues compared with para-tumor tissues by immunohistochemical and western blot assays. Furthermore, Cox proportional hazards regression models, the Kaplan-Meier method, and clinicopathologic features analysis showed that HNRNPC was not only an independent prognostic factor for both overall and disease-free survival in HCC but also a predictor of large tumor size and advanced tumor stage. Functional experiments revealed that silencing of HNRNPC not only led to arrest of more HCC cells at G0/G1 phase to inhibit their proliferation, but also suppressed EMT process to block their invasion, and migration in vitro; this was related to the Ras/MAPK signaling pathway. In addition, blocking of HCC cell proliferation regulated by HNRNPC silencing was observed in vivo. Finally, rescue tests showed that after recovery of Ras/MAPK signaling pathway activity by treatment with Ras agonists, the proliferation, migration, and invasion suppression of Huh-7 and Hep 3B cell lines caused by HNRNPC knockdown was partially reversed. Taken together, these results indicate that HNRNPC knockdown inhibits HCC cell proliferation, migration and invasion, in part via the Ras/MAPK signaling pathway. Thus, HNRNPC may have an important role in the progression of HCC and represents a promising biomarker for evaluation of prognosis and a potential therapeutic target in HCC patients.