Dual targeting of cancer metabolome and stress antigens affects transcriptomic heterogeneity and efficacy of engineered T cells.

Few cancers can be targeted efficiently by engineered T cell strategies. Here, we show that γδ T cell antigen receptor (γδ TCR)-mediated cancer metabolome targeting can be combined with targeting of cancer-associated stress antigens (such as NKG2D ligands or CD277) through the addition of chimeric co-receptors. This strategy overcomes suboptimal γ9δ2 TCR engagement of αß T cells engineered to express a defined γδ TCR (TEGs) and improves serial killing, proliferation and persistence of TEGs. In vivo, the NKG2D-CD28WT chimera enabled control only of liquid tumors, whereas the NKG2D-4-1BBCD28TM chimera prolonged persistence of TEGs and improved control of liquid and solid tumors. The CD277-targeting chimera (103-4-1BB) was the most optimal co-stimulation format, eradicating both liquid and solid tumors. Single-cell transcriptomic analysis revealed that NKG2D-4-1BBCD28TM and 103-4-1BB chimeras reprogram TEGs through NF-κB. Owing to competition with naturally expressed NKG2D in CD8+ TEGs, the NKG2D-4-1BBCD28TM chimera mainly skewed CD4+ TEGs toward adhesion, proliferation, cytotoxicity and less exhausted signatures, whereas the 103-4-1BB chimera additionally shaped the CD8+ subset toward a proliferative state.

Association between dietary inflammatory potential and mortality after cancer diagnosis in the Women's Health Initiative.

BACKGROUND: Chronic inflammation is implicated in cancer prognosis and can be modulated by diet. We examined associations between post-diagnosis dietary inflammatory potential and mortality outcomes among post-menopausal women diagnosed with cancer in the Women's Health Initiative (WHI). METHODS: Energy-adjusted dietary inflammatory index scores (E-DII) were calculated from dietary and supplemental intake data collected on the first food frequency questionnaire following the diagnosis of primary invasive cancer for 3434 women in the WHI. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for risk of death from any cause, cancer, cardiovascular disease (CVD) and other causes by post-diagnosis quartiles of E-DII. Subgroup analyses by cancer stage and grade were performed. RESULTS: There were 1156 deaths after a median 13 years of follow-up from the date of a cancer diagnosis. In the multivariable-adjusted analyses, a more anti-inflammatory diet plus supplements after cancer diagnosis was associated with lower all-cause mortality, cancer mortality, CVD mortality and mortality from other causes with HRsQ1vs.Q4 ranging from 0.47 to 0.68 (all P-trends < 0.05). Associations were stronger for cancers diagnosed at more distant stages or moderately differentiated grades. CONCLUSION: A more anti-inflammatory diet plus supplements after a cancer diagnosis may improve survival for post-menopausal cancer survivors.

Depletion of microRNA-92a Enhances the Role of Sevoflurane Treatment in Reducing Myocardial Ischemia-Reperfusion Injury by Upregulating KLF4.

OBJECTIVE: As some articles have highlighted the role of microRNA-92a (miR-92a) in myocardial ischemia-reperfusion injury (MI/RI), this article aimed to investigate the effect of miR-92a on Sevoflurane (Sevo)-treated MI/RI via regulation of Krüppel-like factor 4 (KLF4). METHODS: An MI/RI rat model was established by ligating the left anterior descending coronary artery. The cardiac function, pathological changes of myocardial tissues, inflammatory response, oxidative stress and cardiomyocyte apoptosis in MI/RI rats were determined. KLF4 and miR-92a expression was detected in the myocardial tissue of rats, and the target relationship between miR-92a and KLF4 was confirmed. RESULTS: Sevo treatment alleviated myocardial damage, inflammatory response, oxidative stress response, and cardiomyocyte apoptosis, and improved cardiac function in MI/RI rats. miR-92a increased and KLF4 decreased in the myocardial tissue of MI/RI rats. KLF4 was targeted by miR-92a. Downregulation of miR-92a or upregulation of KLF4 further enhanced the effect of Sevo treatment on MI/RI. CONCLUSION: This study suggests that depletion of miR-92a promotes upregulation of KLF4 to improve cardiac function, reduce cardiomyocyte apoptosis and further enhance the role of Sevo treatment in alleviating MI/RI.

Prevalence of and risk factors for chronic kidney disease in ten metropolitan areas of China: a cross-sectional study using three kidney damage markers.

INTRODUCTION: To estimate the up-to-date prevalence of chronic kidney disease among the health check-up population in economically developed areas of China using estimated glomerular filtration rate, urinary albumin creatinine ratio, and kidney ultrasound. METHODS: Healthcare data from 38,093 subjects in 10 megalopolises of China who had an annual health check-up in 2021 were used. The overall and stratified prevalence of chronic kidney disease by sex, age, region and comorbidity group was reported. The association between chronic kidney disease and covariates of demographics, and comorbidities were analyzed in the multivariable-adjusted logistic regression model. RESULTS: A total of 3837 CKD cases were detected meeting any of the three CKD diagnostic criteria, with a crude prevalence of 10.1% in the study population. Using one criterion of decreased glomerular filtration rate, albuminuria and kidney structural abnormalities alone detected 204 (5.3%), 3289 (85.7%) and 563 (14.7%) cases, respectively. The addition of kidney ultrasound detected 427 (11.1%) structural abnormality cases without decreased GFR and albuminuria. The most common abnormalities were renal masses, hydronephrosis due to obstruction and congenital anomalies of kidney and urinary tract. Female, older age, low city-tier, hypertension, diabetes, obesity, hypertriglyceridemia as well as early disease stages such as pre-hypertension, impaired fasting glucose and overweight were significantly associated with chronic kidney disease. CONCLUSION: Kidney ultrasound helps to amplify the detection of CKD patients, which is a supplement to kidney function and urine protein.

The efficacy of subgingival air polishing and subgingival debridement in periodontal support therapy: a meta-analysis.

OBJECTIVE: To assess whether there is sufficient evidence of a difference in efficacy between subgingival air polishing (SubAP) and subgingival debridement as periodontal support treatment. The systematic review protocol was registered in the PROSPERO database under no. CRD42020213042. METHODS: A comprehensive search was conducted using eight online databases to develop straightforward clinical questions and search strategies, from their inception to 27 January 2023. The references of identified reports were also retrieved for inclusion in the analysis. The risk-of-bias of the included studies was evaluated using the Revised Cochrane Risk-of-Bias tool (RoB 2). A meta-analysis was performed on five clinical indicators using the Stata 16 software. RESULTS: Twelve randomized controlled trials were ultimately included, and most included studies had varying degrees of risk-of-bias. The results of the meta-analysis indicated that there was no significant difference between SubAP and subgingival scaling in terms of improving probing depth (PD), clinical attachment loss (CAL), plaque index (PLI), and bleeding on probing% (BOP%). The results of the visual analogue scale score analysis indicated that SubAP produced less discomfort than did subgingival scaling. DISCUSSION: SubAP can provide better treatment comfort than subgingival debridement. There was no significant difference in the efficacy of the two modalities in improving PD, CAL, and BOP% in supportive periodontal therapy. CONCLUSION: Currently, evidence for assessing the difference in the efficacy of SubAP and subgingival debridement in improving the PLI is insufficient, and further high-quality clinical studies are needed.

Dietary N-Nitroso Compounds and Risk of Hepatocellular Carcinoma: A USA-Based Study.

BACKGROUND AND AIMS: N-nitroso compounds (NOCs) are among the most potent dietary carcinogens. N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosopiperidine (NPIP) are abundant in foods and carcinogenic to the liver. We investigated the relationship between dietary NOCs and HCC risk. APPROACH AND RESULTS: In this large, hospital-based, case-control study of 827 pathologically or radiologically confirmed HCC cases and 1,013 controls, NOC intake was calculated by linking food frequency questionnaire-derived dietary data with a comprehensive NOC concentration database. Multivariable-adjusted ORs and 95% CIs of HCC by quartiles of NOC consumption were estimated using logistic regression models, with the lowest quartile as the referent. We further investigated joint effects of consuming the highest quartile of NOCs that were associated with increased HCC risk and hepatitis, diabetes, or alcohol drinking on HCC risk. After adjustment for confounding factors, higher intake of NDEA from plant sources (ORQ4 vs. Q1  = 1.58; 95% CI = 1.03-2.41), NDMA from plant sources (ORQ4 vs. Q1  = 1.54; 95% CI = 1.01-2.34), and NPIP (ORQ4 vs. Q1  = 2.52; 95% CI = 1.62-3.94) was associated with increased HCC risk. No association was observed for nitrate or total NOC intake and HCC risk. Higher consumption of HCC-inducing NOCs and positive hepatitis virus status jointly increased the risk of developing HCC. CONCLUSIONS: In conclusion, though some of our findings may indicate the presence of reverse causation owing to lower meat intake among cases with chronic liver diseases before HCC diagnosis, the potent dietary HCC carcinogens, NDEA, NDMA, and NPIP, and their enhanced carcinogenic effects among chronic carriers of hepatitis virus warrant further prospective investigation.

Dietary Intake of Fatty Acids and Risk of Pancreatic Cancer: A Case-Control Study.

BACKGROUND: Epidemiological findings on dietary fat intake and risk of pancreatic cancer (PanC) are inconsistent. OBJECTIVES: This study aimed to determine the association between types of dietary fat intake and PanC. METHODS: We conducted a hospital-based case-control study in 957 pathologically confirmed PanC cases and 938 cancer-free controls. Cases and controls were frequency matched by age, sex, and race. Dietary information was collected using a self-administered validated FFQ. Unconditional logistic regression models were used to estimate the ORs and 95% CIs of PanC risk by quintiles of fat intake with the lowest quintile as referent and with adjustment for other risk factors and dietary factors. RESULTS: We observed no difference in (median) intake of total fat standardized for energy among cases versus controls. The multivariable-adjusted OR (95% CI) of the highest versus the lowest quintile of intake (ORQ5 compared with Q1) was 2.51 (1.68-3.72) for fat from animal sources and 0.41 (0.29-0.58) for fat from plant sources. Intakes of total MUFA, total PUFA, and linoleic (n-6) and long chain n-3 fatty acids were inversely associated with PanC (ORQ5 compared with Q1 and 95% CI: 0.55 [0.36-0.82], 0.59 [0.42-0.82], 0.64 [0.43-0.84], and 0.60 [0.42-0.84], respectively). Arachidonic acid (n-6) and several SFAs were positively associated with PanC. CONCLUSION: Although some observed associations with pancreatic cancer risk could be explained by reverse causation, the potential protective associations with intakes of largely plant-derived PUFAs and MUFAs and fish-derived long chain n-3 PUFAs warrant further prospective investigation.

One-Pot Rapid Access to Benzyl Silanes, Germanes, and Stannanes from Toluenes Mediated by a LiN(SiMe3)2/CsCl System.

Organo-silanes, germanes, and stannanes are considered to be conducive to the development of cross-coupling reactions because they are stable, nontoxic, and easy to handle. Using feedstock toluenes, one-pot direct benzylic C-H silylations, germylations, and stannylations are developed. Simply combining toluenes, LiN(SiMe3)2/CsCl, and R3MCl (M = Si, Ge, Sn) generates a diverse array of bench-stable benzyl silanes, germanes, and stannanes (38 examples, 53-90% yields). The syntheses developed here are easy to access on scale.

Correlation between single nucleotide polymorphisms in CXCR4 microRNA binding site and the susceptibility to knee osteoarthritis in Han Chinese population.

BACKGROUND: This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) at the microRNA target sequence in CXCR4 and the susceptibility to knee osteoarthritis (KOA). METHODS: A total of 305 patients with KOA and 305 healthy controls were recruited into this study. The genotypes of CXCR4 rs1804029 and rs17848060 loci were analyzed. RESULTS: The susceptibility to KOA of CXCR4 rs1804029 G allele carriers was 1.33 times (95% CI: 1.09-1.54, P = .006) that of T allele carriers. The KOA susceptibility in individuals carrying T allele at CXCR4 rs17848060 locus was 1.38 times that of individuals carrying A allele (95% CI: 1.17-1.57, P < .001). The G allele at CXCR4 rs1804029 locus was the target of hsa-miR-146a-3p, while the A allele at CXCR4 rs17848060 locus could be targeted by hsa-miR-20a-3p. The plasma level of hsa-miR-146a-3p was lower in rs1804029 G allele carriers than T allele carriers (P < .001), whereas plasma level of hsa-miR-20a-3p was higher in rs17848060 T allele carriers than A allele carriers (P < .001). CONCLUSION: The SNPs at rs1804029 and rs17848060 loci in CXCR4 were significantly associated with the susceptibility to KOA in Han Chinese population.

Nursing strategies for COVID-19 prevention and control in a selected dental clinic.

AIM: To comprehensively introduce the prevention and control measures that we can take in dental clinics during the pandemic period of coronavirus disease 2019 (COVID-19) and provide some practical experience for the development of nursing and health policies applicable to COVID-19. BACKGROUND: The outbreak of COVID-19 has placed the global health system under threat, which seriously influences the normal operations of human society. Safe and effective nursing measures should be taken to ensure the normal operation of dental clinics. SOURCES OF EVIDENCE: We searched and referenced many references on the PubMed database. Through the combination of related literatures and our experience, we describe various strategies, including personnel management, personal protection, disinfection and isolation, adopted in the dental clinic of our Chinese hospital during the pandemic of COVID-19. DISCUSSION/CONCLUSIONS: We introduced strategies for the nursing staff in dental clinics to assist them with the prevention and control of COVID-19. The successful implementation of the protective measures could ensure the safety of medical staff and patients, and contributed to the normal operation of dental clinics during the pandemic period. CONCLUSIONS FOR NURSING AND HEALTH POLICY: During the pandemic, frontline nurses are under physical and mental pressure facing the threat of infection while at work. In addition to pandemic prevention, we should also pay attention to the needs of nursing staff. More reasonable and effective nursing and health policies should be formulated to ensure their safety and protect their rights and interests. This is the only way that the prevention and control of COVID-19 can be achieved, and we can prepare for future public health events.

Dietary inflammatory potential in relation to the gut microbiome: results from a cross-sectional study.

Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and ß-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.

Post-cancer diagnosis dietary inflammatory potential is associated with survival among women diagnosed with colorectal cancer in the Women's Health Initiative.

PURPOSE: Dietary factors may influence colorectal cancer (CRC) survival through effects on inflammation. We examined the association between post-CRC diagnosis inflammatory potential of diet and all-cause and cancer-specific mortality in the Women's Health Initiative. METHODS: The study included 463 postmenopausal women who developed CRC during follow-up and completed a food frequency questionnaire (FFQ), on average 1.7 years after diagnosis. Women were followed from CRC diagnosis until death, censoring, or the end of follow-up in October 2014. Energy-adjusted dietary inflammatory index (E-DII)® scores were calculated from the FFQ and dietary supplement inventory. Cox proportional hazards models were fitted to estimate multivariable-adjusted HRs and 95% confidence intervals (CIs) for all-cause, total cancer, and CRC-specific mortality with the most pro-inflammatory E-DII scores (tertile 3) as referent. RESULTS: After a median 11.6 years of follow-up, 162 deaths occurred, including 77 from CRC. Lowest tertile (i.e., most anti-inflammatory) E-DII scores from diet plus supplements were associated with significantly lower all-cause mortality (HRT1vsT3 = 0.49; 95% CI 0.31-0.79) compared to the most pro-inflammatory E-DII tertile. Modest associations with total cancer mortality or CRC-specific mortality were observed, though 95% CIs included 1. CONCLUSIONS: Consuming a dietary pattern and supplements with more anti-inflammatory potential after CRC diagnosis may improve overall survival among postmenopausal women.

Dietary N-nitroso compounds and risk of pancreatic cancer: results from a large case-control study.

N-nitroso compounds (NOCs) are among the most potent dietary and pancreatic carcinogens. N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) are the most prevalent NOCs identified in foods. Using a validated and comprehensive N-nitroso database developed to estimate total NOCs and important individual NOCs from food intake, we investigated dietary exposure to NOCs in relation to pancreatic cancer in a large matched case-control study. Self-administered food frequency questionnaires were collected from 957 pathologically confirmed pancreatic ductal adenocarcinoma cases and 938 frequency-matched controls. For each food item, frequency of intake and portion size in grams was multiplied by the estimated NOC concentration from the N-nitroso database. Multiple unconditional logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CIs) for pancreatic cancer risk by quartiles of NOCs and major food group contributors to NOCs, with the lowest quartile as referent. Following adjustment for confounders, we observed significant positive associations for NDEA (ORQ4 versus Q1 = 2.28, 95% CI = 1.71-3.04, Ptrend < 0.0001) and NDMA from plant sources (ORQ4 versus Q1 = 1.93, 95% CI = 1.42-2.61, Ptrend < 0.0001) with pancreatic cancer. The major food groups related to NDEA and NDMA intakes in this population were fermented cheese, pizza, grains, seafood and beer. No associations of intake of nitrate or total NOCs were observed; nitrite was inversely associated with pancreatic cancer. Although some of our findings probably reflect reverse causation bias due to lower meat intake in cases with latent disease, biologically plausible findings for pancreatic carcinogens, NDEA and NDMA, warrant further prospective investigation.

Diet quality and Gleason grade progression among localised prostate cancer patients on active surveillance.

BACKGROUND: High diet quality may support a metabolic and anti-inflammatory state less conducive to tumour progression. We prospectively investigated diet quality in relation to Gleason grade progression among localised prostate cancer patients on active surveillance, a clinical management strategy of disease monitoring and delayed intervention. METHODS: Men with newly diagnosed Gleason score 6 or 7 prostate cancer enroled on a biennial monitoring regimen. Patients completed a food frequency questionnaire (FFQ) at baseline (n = 411) and first 6-month follow-up (n = 263). Cox proportional hazards models were fitted to evaluate multivariable-adjusted associations of diet quality [defined via the Healthy Eating Index (HEI)-2015] with Gleason grade progression. RESULTS: After a median follow-up of 36 months, 76 men progressed. Following adjustment for clinicopathologic factors, we observed a suggestive inverse association between baseline diet quality and Gleason grade progression [hazard ratio (HR) and 95% confidence interval (CI) for the highest vs. the lowest HEI-2015 tertile: 0.59 (0.32-1.08); Ptrend = 0.06]. We observed no associations with diet quality at 6-month follow-up, nor change in diet quality from baseline. CONCLUSIONS: In localised prostate cancer patients on surveillance, higher diet quality or conformance with United States dietary guidelines at enrolment may lower risk of Gleason grade progression, though additional confirmatory research is needed.

Coffee, Caffeine Metabolism Genotype and Disease Progression in Patients with Localized Prostate Cancer Managed with Active Surveillance.

PURPOSE: Active surveillance is increasingly used as a management strategy for localized prostate cancer. Coffee intake has been associated with a lower prostate cancer incidence. We assessed whether coffee was associated with disease progression in men on active surveillance. MATERIALS AND METHODS: A total of 411 patients with newly diagnosed Gleason score 6 or 7 prostate cancer were enrolled on a prospective active surveillance protocol for at least 6 months and completed a baseline dietary assessment. The active surveillance protocol included a biennial monitoring regimen with disease progression defined as an increase in the Gleason score. Cox proportional hazards models were used to evaluate associations of coffee intake with progression-free survival. We also evaluated patient genotype in the caffeine metabolism related single nucleotide polymorphism rs762551. RESULTS: Median followup was 36 months (range 6 to 126) and the Gleason score progressed in 76 of the 411 patients (18.5%). Compared to 0 cups per day, in the multivariable model adjusting for prostate specific antigen, patient age and tumor length, less than 1 cup (HR 0.85, 95% CI 0.40-1.71), 1 to 1.9 cups (HR 0.64, 95% CI 0.29-1.43), 2 to 3.9 cups (HR 0.71, 95% CI 0.35-1.47) and 4 cups or more (HR 1.67, 95% CI 0.81-3.45) were not significantly associated with progression-free survival (p for nonlinearity = 0.01). Patients with low/moderate coffee intake and the AA fast caffeine metabolizer genotype were less likely to experience grade progression than nonconsumers (HR 0.36, 95% CI 0.15-0.88, p = 0.03). CONCLUSIONS: Low to moderate coffee intake appears safe in men on active surveillance of localized prostate cancer. Further work is needed to determine whether high consumption is associated with shorter progression-free survival in sensitive groups.

Vitamin C and Vitamin E Mitigate the Risk of Pancreatic Ductal Adenocarcinoma from Meat-Derived Mutagen Exposure in Adults in a Case-Control Study.

BACKGROUND: Previous studies have found that meat-derived mutagens increase, and vitamin C or E decrease, the risk of pancreatic cancer. OBJECTIVE: The aim of this study was to determine whether intake of vitamin C or E modulates the association between meat-derived mutagen exposure and risk of pancreatic cancer. DESIGN: We conducted a case-control study in 1321 patients with pathologically confirmed pancreatic ductal adenocarcinoma (PDAC) and 1061 healthy controls (aged 28-88 y). Cases and controls were frequency-matched by age, sex, and race/ethnicity. Mutagen intake was assessed using a meat preparation questionnaire. Intakes of vitamin C, E, and other dietary components were assessed via a food-frequency questionnaire in a subset of 811 cases and 818 controls. ORs and 95% CIs were estimated in multivariable-adjusted logistic regression models. RESULTS: The risk of PDAC was not associated with meat intake but was associated with consumption of well-done grilled or barbecued chicken (OR: 1.57; 95% CI: 1.18, 2.09; P = 0.001). Intake of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline was associated with increased PDAC risk (Ptrend = 0.047). Participants in the highest, as compared with the lowest, quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (PhIP) intake experienced a 38% increased risk of PDAC (95% CI: 1.00, 1.90; P = 0.048). Intakes of total vitamin C or E from food and supplements or from supplements alone were each inversely associated with PDAC risk. Stratified analyses showed differential associations for PhIP intake and PDAC risk, such that risk increased among individuals with lower intake of vitamin C or E and decreased among those with higher vitamin intake. Significant interactions of dietary vitamin C, dietary vitamin E, and total vitamin E with PhIP intake were detected (Pinteraction = 0.023, <0.001, and 0.013, respectively). CONCLUSIONS: Consistent with experimental evidence, this study of 811 cases and 818 controls has shown that high intake of dietary vitamin C or E mitigates the risk of PhIP-related PDAC.

Gut microbial diversity and genus-level differences identified in cervical cancer patients versus healthy controls.

OBJECTIVES: The aim of this study was to characterize variation in the gut microbiome of women with locally advanced cervical cancer and compare it to healthy controls. METHODS: We characterized the 16S rDNA fecal microbiome in 42 cervical cancer patients and 46 healthy female controls. Shannon diversity index (SDI) was used to evaluate alpha (within sample) diversity. Beta (between sample) diversity was examined using principle coordinate analysis (PCoA) of unweighted Unifrac distances. Relative abundance of microbial taxa was compared between samples using Linear Discriminant Analysis Effect Size (LEfSe). RESULTS: Within cervical cancer patients, bacterial alpha diversity was positively correlated with age (p = 0.22) but exhibited an inverse relationship in control subjects (p < 0.01). Alpha diversity was significantly higher in cervical cancer patients as compared to controls (p < 0.05), though stratification by age suggested this relationship was restricted to older women (>50 years; p < 0.01). Beta diversity (unweighted Unifrac; p < 0.01) also significantly differed between cervical cancer patients and controls. Based on age- and race-adjusted LEfSe analysis, multiple taxa significantly differed between cervical cancer patients and controls. Prevotella, Porphyromonas, and Dialister were significantly enriched in cervical cancer patients, while Bacteroides, Alistipes and members of the Lachnospiracea family were significantly enriched in healthy subjects. CONCLUSION: Our study suggests differences in gut microbiota diversity and composition between cervical cancer patients and controls. Associations within the gut microbiome by age may reflect etiologic/clinical differences. These findings provide rationale for further study of the gut microbiome in cervical cancer.

Dietary protein intake and risk of type 2 diabetes: a dose-response meta-analysis of prospective studies.

PURPOSE: The association between dietary protein intake and type 2 diabetes risk has been inconsistent in the previous epidemiological studies. We aimed to quantitatively assess whether dietary total, animal, and plant protein would be associated with type 2 diabetes risk. METHODS: A comprehensive literature review was conducted to identify related articles by searching PubMed, Embase, Web of Science, and Wiley Online Library through 20th March 2018. Generalized least squares for trend estimation and restricted cubic spline regression model were applied in the dose-response analysis. RESULTS: Eight publications with ten prospective cohorts of 34,221 type 2 diabetes cases were included. After adjustment of potential confounders, a 5% of energy increment from dietary total and animal protein intake was related to a 9% (1.04, 1.13; I2 = 42.0%) and 12% (95% CI 1.08, 1.17; I2 = 14.0%) higher risk of type 2 diabetes respectively. However, for plant protein, a significant U-shaped curve was observed with the most risk reduction at intake of about 6% of energy intake from plant protein intake (Pnonlinearity = 0.001). The results were robust in sensitivity analysis and no publication bias was detected. CONCLUSIONS: These findings indicate that the consumption of protein particularly animal protein may be associated with an increased risk of type 2 diabetes.

Inflammatory potential of diet and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

Inflammation plays a central role in pancreatic cancer etiology and can be modulated by diet. We aimed to examine the association between the inflammatory potential of diet, assessed with the Dietary Inflammatory Index (DII®), and pancreatic cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial prospective cohort. Our study included 101,449 participants aged 52-78 years at baseline who completed both baseline questionnaire and a diet history questionnaire. Energy-adjusted DII (E-DII) scores were computed based on food and supplement intake. Cox proportional hazards models and time dependent Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with participants in the lowest E-DII quintile (most anti-inflammatory scores) as referent. After a median 8.5 years of follow-up, 328 pancreatic cancer cases were identified. E-DII scores were not associated with pancreatic cancer risk in the multivariable model (HRQ5vsQ1 = 0.94; 95% CI = 0.66-1.35; p-trend = 0.43). Time significantly modified the association (p-interaction = 0.01). During follow up <4 years, there was suggestive evidence of an inverse association between E-DII and pancreatic cancer (HRQ5vsQ1  = 0.60; 95% CI = 0.35-1.02; p-trend = 0.20) while there was a significant positive trend in the follow up ≥4 years (HRQ5vsQ1 = 1.31; 95% CI = 0.83-2.08; p-trend = 0.03). Similar results were observed for E-DII from food only. Our study does not support an association between inflammatory potential of diet and pancreatic cancer risk; however, heterogeneous results were obtained with different follow-up times. These divergent associations may result from the influences of undetected disease in the short-term.

Risk prediction models for hepatocellular carcinoma in different populations.

Hepatocellular carcinoma (HCC) is a malignant disease with limited therapeutic options due to its aggressive progression. It places heavy burden on most low and middle income countries to treat HCC patients. Nowadays accurate HCC risk predictions can help making decisions on the need for HCC surveillance and antiviral therapy. HCC risk prediction models based on major risk factors of HCC are useful and helpful in providing adequate surveillance strategies to individuals who have different risk levels. Several risk prediction models among cohorts of different populations for estimating HCC incidence have been presented recently by using simple, efficient, and ready-to-use parameters. Moreover, using predictive scoring systems to assess HCC development can provide suggestions to improve clinical and public health approaches, making them more cost-effective and effort-effective, for inducing personalized surveillance programs according to risk stratification. In this review, the features of risk prediction models of HCC across different populations were summarized, and the perspectives of HCC risk prediction models were discussed as well.