Association of total and different food-derived advanced glycation end-products with risks of all-cause and cause-specific mortality.

Background: advanced glycation end-products (AGEs), formed through a series of non-enzymatic reactions, can promote inflammation and oxidative stress. Their accumulation in the body has been linked to cardiovascular disease (CVD) and cancer. However, the association of total AGEs and AGEs from different food sources with risks of all-cause, CVD, and cancer mortality is still unknown. Methods: we conducted a prospective cohort study of a nationally representative sample of 22 124 participants from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2003-2006. A food frequency questionnaire (FFQ) was utilized to calculate total and different food-derived AGE intake. Associations between various dietary AGE scores and the risk of all-cause, CVD, and cancer mortality were assessed by weighted Cox proportional hazard regression models. Results: over a median follow-up period of 27.1 years, we found that in the general population, AGE scores of both baked foods and meat were risk factors for all-cause, CVD, and cancer mortality. Specially, higher AGE scores in total and those derived from 10 of the 13 food groups were statistically associated with an increased risk of CVD mortality. Egg-, fruit-, and vegetable-derived AGE scores were positively correlated with the risk of cancer mortality. Additionally, there were positive multiplicative and additive interactions between smoking and meat-derived AGE scores on all-cause mortality. Conclusions: high amounts of AGE consumption is associated with an increased risk of CVD mortality, and meat and baked food-derived AGEs were positively linked to all-cause, CVD, and cancer mortalities. Adherence to unhealthy lifestyles, such as smoking, may increase mortality from leading causes in individuals with AGE-enriched diet habits.

Extracellular vesicles from 3D cultured dermal papilla cells improve wound healing via Krüppel-like factor 4/vascular endothelial growth factor A -driven angiogenesis.

Background: Non-healing wounds are an intractable problem of major clinical relevance. Evidence has shown that dermal papilla cells (DPCs) may regulate the wound-healing process by secreting extracellular vesicles (EVs). However, low isolation efficiency and restricted cell viability hinder the applications of DPC-EVs in wound healing. In this study, we aimed to develop novel 3D-DPC spheroids (tdDPCs) based on self-feeder 3D culture and to evaluate the roles of tdDPC-EVs in stimulating angiogenesis and skin wound healing. Methods: To address the current limitations of DPC-EVs, we previously developed a self-feeder 3D culture method to construct tdDPCs. DPCs and tdDPCs were identified using immunofluorescence staining and flow cytometry. Subsequently, we extracted EVs from the cells and compared the effects of DPC-EVs and tdDPC-EVs on human umbilical vein endothelial cells (HUVECs) in vitro using immunofluorescence staining, a scratch-wound assay and a Transwell assay. We simultaneously established a murine model of full-thickness skin injury and evaluated the effects of DPC-EVs and tdDPC-EVs on wound-healing efficiency in vivo using laser Doppler, as well as hematoxylin and eosin, Masson, CD31 and α-SMA staining. To elucidate the underlying mechanism, we conducted RNA sequencing (RNA-seq) of tdDPC-EV- and phosphate-buffered saline-treated HUVECs. To validate the RNA-seq data, we constructed knockdown and overexpression vectors of Krüppel-like factor 4 (KLF4). Western blotting, a scratch-wound assay, a Transwell assay and a tubule-formation test were performed to detect the protein expression, cell migration and lumen-formation ability of KLF4 and vascular endothelial growth factor A (VEGFA) in HUVECs incubated with tdDPC-EVs after KLF4 knockdown or overexpression. Dual-luciferase reporter gene assays were conducted to verify the activation effect of KLF4 on VEGFA. Results: We successfully cultured tdDPCs and extracted EVs from DPCs and tdDPCs. The tdDPC-EVs significantly promoted the proliferation, lumen formation and migration of HUVECs. Unlike DPC-EVs, tdDPC-EVs exhibited significant advantages in terms of promoting angiogenesis, accelerating wound healing and enhancing wound-healing efficiency both in vitro and in vivo. Bioinformatics analysis and further functional experiments verified that the tdDPC-EV-regulated KLF4/VEGFA axis is pivotal in accelerating wound healing. Conclusions: 3D cultivation can be utilized as an innovative optimization strategy to effectively develop DPC-derived EVs for the treatment of skin wounds. tdDPC-EVs significantly enhance wound healing via KLF4/VEGFA-driven angiogenesis.

Associations of physical frailty with incidence and mortality of overall and site-specific cancers: A prospective cohort study from UK biobank.

OBJECTIVE: Evidence regarding the role of physical frailty in cancer-related outcomes is limited. We aimed to examine the association of frailty with cancer incidence and mortality risk. METHODS: This prospective study included 348,144 participants free of cancer at baseline from the UK Biobank. Frailty phenotypes (non-frail, pre-frail, and frail) were constructed from 5 components: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The outcome was incidence and mortality of overall and cite-specific cancers. Cox proportional hazard regression was used to estimate the association of frailty phenotypes with cancer incidence and mortality risk. RESULTS: A total of 43,304 incident cancer cases and 10,152 cancer deaths were documented during a median of 12.0 years of follow-up. For overall cancer, compared with non-frailty, the incidence risk increased by 4% for pre-frailty and 11% for frailty, and the mortality risk increased by 11% for pre-frailty and 39% for frailty. Frailty phenotypes were also dose-dependently associated with a higher risk of incidence and mortality of some site-specific cancers (including liver and lung), with significant sex differences. We observed a synergetic association of frailty phenotypes and smoking with overall cancer incidence and mortality risk. CONCLUSIONS: Frailty phenotypes contributed significantly to a higher risk of overall and some site-specific cancers incidence and mortality in a stepwise manner or within individual categories. Future studies are warranted to emphasize the identification, management and prevention of frailty in the whole population and complements of lifestyle-targeted interventions such as quitting smoking.

Association between diabetes at different diagnostic ages and risk of cancer incidence and mortality: a cohort study.

Background: Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37-73 years. Methods: Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41-50, 51-60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses. Results: Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41-50, 51-60, and >60 years, especially at 51-60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51-60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088-2.416, HR for mortality: 1.276-3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51-60 years. Conclusion: Our findings highlighted that the age at diagnosis of diabetes, especially 51-60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer.

Plant-based dietary patterns, genetic predisposition and risk of colorectal cancer: a prospective study from the UK Biobank.

BACKGROUND: Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk. METHODS: This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model. RESULTS: Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81-0.96) and 0.91 (95% CI, 0.84-0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males. CONCLUSIONS: Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.

Plasma One-Carbon Metabolism-Related Micronutrients and the Risk of Breast Cancer: Involvement of DNA Methylation.

Findings of epidemiologic studies focusing on the association between one-carbon metabolism-related micronutrients and breast cancer risk, along with the involvement of DNA methylation, have been inconsistent and incomprehensive. We conducted a case-control study in China including 107 paired participants and comprehensively detected 12 plasma one-carbon metabolism-related micronutrients. Genomic DNA methylation was measured using an 850 K chip and differential methylation probes (DMPs) were identified. Multivariate logistic regression was performed to estimate the associations between plasma micronutrients and the odds of breast cancer. The mediation of selected DMPs in micronutrient breast cancer associations was examined using mediation analyses. An inverse association of plasma folate, methionine cycling-related micronutrients (methionine, S-adenosylmethionine, and S-adenosylhomocysteine), and all micronutrients in the choline metabolism and enzymatic factor groups, and a positive association of methionine cycling-related cysteine with breast cancer risk were observed. Nine micronutrients (methionine, cysteine, SAM, folate, choline, betaine, P5P, vitamins B2, and B12) were related to global or probe-specific methylation levels (p < 0.05). The selected DMPs mediated the micronutrient breast cancer associations with an average mediation proportion of 36.43%. This study depicted comprehensive associations between circulating one-carbon metabolism-related micronutrients and breast cancer risk mediated by DNA methylation.

Association between the Finnish Diabetes Risk Score and cancer in middle-aged and older adults: Involvement of inflammation.

BACKGROUND: Diabetes is associated with increased risk of common cancers. However, evidence of cancer risk in individuals with different diabetes risk is still scarce, and the underlying mechanism remains unknown. Therefore, we aimed to evaluate the relationship between the Finnish Diabetes Risk Score (FINDRISC) and risks of cancer incidence and mortality in a prospective study, and to explore whether low-grade inflammation partially mediated the association. METHODS: A total of 330,384 participants aged 37 to 73 at baseline from the UK Biobank database was included in this study. The Cox proportional hazards model was used to examine the relationship of the FINDRISC and low-grade inflammation with risks of cancer incidence and mortality. Then, we estimated the contribution of higher FINDRISC to risks of overall and site-specific cancers. In addition, the role of low-grade inflammation in the association between FINDRISC and cancer risks was investigated through mediation analysis. RESULTS: The increased FINDRISC was dose-dependently associated with higher incidence and mortality risks of overall cancer and an overwhelming majority of site-specific cancers. The higher FINDRISC was a strong contributor to incidence of eighteen site-specific cancers and mortality of fourteen site-specific cancers, with a population-attributable risk of 8.1 %-39.1 %, 14.2 %-39.7 %, respectively. Additionally, low-grade inflammation mainly mediated the association between the FINDRISC and risks of incidence and mortality of overall cancer, colorectal cancer, etc. CONCLUSIONS: Our findings highlighted the higher FINDRISC as critical risk factors of cancer incidence and mortality, partially mediated by low-grade inflammation. Individuals with increased risk of diabetes are also needed to be concerned about cancer prevention.

Rs11479 in Thymidine Phosphorylase Associated with Prognosis of Patients with Colorectal Cancer Who Received Capecitabine-Based Adjuvant Chemotherapy.

Objective: Thymidine Phosphorylase (TYMP) gene was of potential significance in the process of colorectal cancer (CRC) development and played an important role in capecitabine metabolism. This study was to identify the association between TYMP polymorphism and prognosis of postoperative patients with CRC who received capecitabine-based adjuvant chemotherapy. Methods: A total of 218 patients with CRC who were treated with surgical resection and capecitabine-based adjuvant chemotherapy were included in this study retrospectively. Peripheral blood and peripheral blood mononuclear cell (PBMC) specimen of the patients were collected for the genotyping of TYMP polymorphism and TYMP mRNA expression, respectively. Univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis, Cox regression analysis was adopted in multivariate analysis. The mRNA expression of TYMP according to genotype status was analyzed using non-parameter test. Results: Prevalence of rs11479 in TYMP among the 218 patients exhibited that minor allele frequency of rs11479 was 0.20 (GG 141 cases, GA 68 cases and AA 9 cases), which was in accordance with Hardy-Weinberg equilibrium (P=0.825). Association analysis suggested that the median disease-free survival (DFS) of patients with GG genotype and GA/AA genotype was 3.1 and 6.1 years, respectively (P=0.004). Furthermore, the median overall survival of patients with GG genotype and GA/AA genotype was 5.0 and 7.0 years, respectively (P=0.033). Multivariate Cox regression analysis exhibited that rs11479 polymorphism was an independent factor for DFS (HR = 1.64, P=0.009). Additionally, of the 65 PBMC specimens, mRNA expression results indicated that patients with GA/AA genotypes conferred significantly higher mRNA expression of TYMP than that of patients with GG genotype (P<0.001). Conclusion: Polymorphism rs11479 in TYMP gene might predict the prognosis of patients with CRC who received capecitabine-based adjuvant chemotherapy through mediation of the mRNA expression of TYMP. The conclusion of this study should be validated in prospective clinical trials subsequently.

Effect of stem cell treatment on burn wounds: A systemic review and a meta-analysis.

A meta-analysis was performed to evaluate the effect of stem cells treatment in managing burn wounds. A systematic literature search up to March 2022 incorporated 24 studies reported between 2013 and 2021 including 400 animals with burn wounds at the beginning of the study; 211 were using stem cells treatment, and 189 controlled. Statistical tools like the contentious method were used within a random or fixed-influence model to establish the mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of stem cells treatment in managing burn wounds. Stem cells treatment had a significantly higher burn wound healing rate (MD, 15.18; 95% CI, 11.29-19.07, P < .001), higher blood vessel number (MD, 12.28; 95% CI, 10.06-14.51, P < .001), higher vascular endothelial growth factor (MD, 10.24; 95% CI, 7.19-13.29, P < .001), lower interleukin-1 level (MD, -98.48; 95% CI, -155.33 to -41.63, P < .001), and lower tumour necrosis factor α level (MD, -28.71; 95% CI, -46.65 to -10.76, P < .002) compared with control in animals' models with burn wounds. Stem cells treatment had a significantly higher burn wound healing rate, higher blood vessel number, higher vascular endothelial growth factor, lower interleukin-1 level, and lower tumour necrosis factor α level compared with control in animals' models with burn wounds. Further studies are required to validate these findings.

Effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer: A meta-analysis.

We performed a meta-analysis to evaluate the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer. A systematic literature search up to March 2022 was performed and 2247 subjects with possibly curative surgery for colorectal cancer at the baseline of the studies; 2889 of them were obese, and 9358 were non-obese. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of body mass index on surgical site wound infection, mortality, and postoperative hospital stay in subjects undergoing possibly curative surgery for colorectal cancer using the dichotomous or contentious methods with a random or fixed-effect model. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery (OR, 1.87; 95% CI, 1.62-2.15, P < .001), and higher mortality (OR, 1.58; 95% CI, 1.07-2.32, P = .02) in subjects with possibly curative surgery for colorectal cancer compared with non-obese. However, obese did not show any significant difference in postoperative hospital stay (MD, 0.81; 95% CI, -0.030 to 1.92, P = .15) compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The obese subjects had a significantly higher surgical site wound infection after colorectal surgery, higher mortality, and no significant difference in postoperative hospital stay compared with non-obese in subjects with possibly curative surgery for colorectal cancer. The analysis of outcomes should be with caution because of the low number of studies in certain comparisons.

Association of serum Klotho levels with cancer and cancer mortality: Evidence from National Health and Nutrition Examination Survey.

BACKGROUND: Klotho has both anticancer and hormone-like functions. But the research on Klotho and cancer is mainly based on animal experiments and small-scale clinical research, thus we explored the association between serum Klotho and cancer and cancer mortality based on the National Health and Nutrition Survey (NHANES). METHODS: Participants were employed from the NHANES 2007-2016, excluding pregnant, chronic renal insufficiency, and incomplete data of cancer questionnaire and serum Klotho level. The association of serum Klotho with cancer and mortality was analyzed by weighted Logistic regression, weighted Cox regression and competitive risk model, respectively. Correlations between serum Klotho and testosterone and estradiol levels were analyzed by Spearman correlation and restricted cubic spline respectively. RESULTS: We found Klotho had an inverse effect with risk of pan-cancer (all p < 0.02), with each unit increase in Klotho (1ug/g creatinine) associated with a 0.9%-2.2% reduction in the risk of cancer, and higher levels showing a stronger negative association (all p-trend <= 0.0005). Whereas, we did not observe any association between serum Klotho level with all-cause mortality and cancer-specific mortality (all p > 0.05). Then, stratified analysis found that people aged 60-79, female, overweight and non-Hispanic whites or Mexican Americans were less likely to develop cancer. In addition, there was a strong nonlinear and linear positive correlation of Klotho with estradiol (p-nonlinear = 0.0178) and testosterone only among male participants (ß = -0.513, p = 0.0137), respectively. CONCLUSIONS: We found an inverse association between serum Klotho and cancer, but without cancer mortality. And this effect may be partially mediated by estradiol and testosterone. Further prospective studies are needed to prove these findings.

Association of urinary phytoestrogens with hormone-related cancers and cancer biomarkers: NHANES 1999-2010.

Phytoestrogens may have potential effects on hormone-related cancers (HRC) and cancer biomarkers, but the findings have been inconsistent so far. Participants from the National Health and Nutrition Examination Survey 1999-2010 with information on the levels of urinary phytoestrogens, serum cancer biomarkers and cancer history were included. Sampling-weighted logistic regression models examined the association between urinary phytoestrogens concentrations (creatinine-standardised and log-transformed) and HRC, followed by stratified analyses by race/ethnicity, age and menopausal status for different gender. Correlation analyses between phytoestrogens and cancer biomarkers were performed. Of the total 8844 participants, there were 373 with HRC. We observed total isoflavone and enterodiol excretion were positively associated with HRC, especially in non-Hispanic white female subpopulations (Ptrend < 0·05). Similar association also existed in the total isoflavones and enterodiol levels with breast cancer. Whereas the highest concentration of total isoflavones was significantly linked to a reduced prevalence of HRC (OR = 0·40, 95 % CI: 0·19, 0·84) in white males and of prostate cancer (OR = 0·40, 95 % CI: 0·18, 0·86). Among twenty-four participants with HRC, urinary equol concentration was positively correlated with CA15.3. Also, an inverse correlation of total prostate-specific antigens (PSA) and positive correlation of the PSA ratio with urinary enterolactone were detected in thirteen prostate cancer patients. Our findings indicated that higher concentrations of total isoflavones and enterodiol were positively associated with HRC. Urinary certain phytoestrogen excretion may affect serum cancer biomarker levels in cancer patients. But further prospective studies are needed to provide stronger evidence.

The Number of Positive Tumor Markers (NPTM) Achieves Higher Value in the Prognosis Prediction of Gastric Cancer.

Purpose: The clinical application of combined tumor markers is still limited. We aim to explore the value of the combination of multiple tumor markers in gastric cancer (GC) prognosis. Methods: The prognostic significance was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The estimated area under the curve (AUC) was compared to evaluate the discriminatory ability of different indicators. A nomogram was constructed based on the results of multivariable cox regression, and its performance was evaluated by Harrell's concordance index and calibration curve. Results: NPTM (number of positive tumor markers) displayed independent prognostic significance whether in the whole cohort or in patients with different stages. Patients with the all-negative tumor markers had a worse prognosis after postoperative chemotherapy in all cohort (P = 0.023) or in age ≤60 subgroup (P = 0.012), while patients with positive tumor markers had a better prognosis after postoperative chemotherapy in stage III (P = 0.012). The AUC value of NPTM is higher than any individual tumor marker. The 1-, 3-, and 5-year AUC values of the CTNM (combination of NPTM and pTNM) increased by 5%, 4.8%, and 3.6%, respectively, compared with TNM staging system. The nomogram constructed including NPTM showed its high accuracy (C - index = 0.706) versus TNM staging system (C - index = 0.646) and CTNM (C - index = 0.681). Conclusions: NPTM was an independent predictor of gastric cancer prognosis, showing more accurate prognostic performance than individual tumor markers. Especially its significance in guiding postoperative adjuvant chemotherapy regimens and predicting prognosis by combination with TNM staging system may have a better clinical application value.

Genetically Modified Circulating Levels of Advanced Glycation End-Products and Their Soluble Receptor (AGEs-RAGE Axis) with Risk and Mortality of Breast Cancer.

The interaction of advanced glycation end-products (AGEs) with their receptor (RAGE) elicits oxidative stress and inflammation, which is involved in the development of breast cancer. However, large-scale population-based evidence exploring genetically modified circulating levels of AGEs-RAGE axis with risk and mortality of breast cancer is scarce. We recruited 1051 pairs of age-matched breast cancers and controls and measured plasma AGEs and sRAGE concentrations by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression and Cox proportional hazard model were used to calculate the effects of plasma levels and genetic variants of the AGEs-RAGE axis and their combined effects on breast cancer risk and prognosis, respectively. Furthermore, linear regression was performed to assess the modifications in plasma AGEs/sRAGE levels by genetic predisposition. Higher levels of AGEs and AGEs/sRAGE-ratio were associated with an increased risk of breast cancer, but sRAGE levels were negatively associated with breast cancer risk, especially in women <60 years. We also observed a positive association between AGEs and the bad prognosis of breast cancer. Although we did not observe a significant contribution of genetic variants to breast cancer risk, rs2070600 and rs1800624 in the AGER gene were dose-dependently correlated with sRAGE levels. Further, compared to the haplotype CT at the lowest quartile of AGEs, haplotypes TT and TA were prominently associated with breast cancer risk in the highest quartile of AGEs. This study depicted a significant association between circulating levels of AGEs-RAGE axis and breast cancer risk and mortality and revealed the potential of plasma AGEs, especially coupled with AGER polymorphism as biomarkers of breast cancer.

Chitosan degradation products promote healing of burn wounds of rat skin.

Burns can impair the barrier function of the skin, and small burns can also cause high mortality. The WHO has described that over 180,000 people die of burns worldwide each year. Thus, the treatment of burn wounds is a major clinical challenge. Chitooligosaccharides (COS) are alkaline amino oligosaccharides with small molecular weights obtained by enzyme or chemical degradation of chitosan. With the characteristics of biocompatibility, water solubility and degradability, it has attracted increasing attention in the fields of biomedicine. In the present study, we used COS to treat deep second-degree burn wounds of rat skin and found that COS was able to promote wound healing. We also revealed that COS could promote fibroblast proliferation. Transcriptome sequencing analysis was performed on COS-treated fibroblasts to identify the underlying mechanisms. The results showed that COS was able to promote wound healing through regulation of the mitogen-activated protein kinase (MAPK) pathway and growth factor Hepatocyte Growth Factor (HGF). Our results provide a potential drug for burn wound therapy and the related molecular mechanism.

Model established based on blood markers predicts overall survival in patients after radical resection of types II and III adenocarcinoma of the esophagogastric junction.

BACKGROUND: In recent years, the incidence of types II and III adenocarcinoma of the esophagogastric junction (AEG) has shown an obvious upward trend worldwide. The prognostic prediction after radical resection of AEG has not been well established. AIM: To establish a prognostic model for AEG (types II and III) based on routine markers. METHODS: A total of 355 patients who underwent curative AEG at The First Affiliated Hospital of Anhui Medical University from January 2014 to June 2015 were retrospectively included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors. A nomogram was constructed based on Cox proportional hazards models. The new score models was analyzed by C index and calibration curves. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the scoring system and tumor-node-metastasis (TNM) stage. Overall survival was calculated using the Kaplan-Meier curve amongst different risk AEG patients. RESULTS: Multivariate analysis showed that TNM stage (hazard ratio [HR] = 2.286, P = 0.008), neutrophil-to-lymphocyte ratio (HR = 2.979, P = 0.001), and body mass index (HR = 0.626, P = 0.026) were independent prognostic factors. The new scoring system had a higher concordance index (0.697), and the calibration curves of the nomogram were reliable. The area under the ROC curve of the new score model (3-year: 0.725, 95% confidence interval [CI]: 0.676-0.777; 5-year: 0.758, 95%CI: 0.708-0.807) was larger than that of TNM staging (3-year: 0.630, 95%CI: 0.585-0.684; 5-year: 0.665, 95%CI: 0.616-0.715). CONCLUSION: Based on the serum markers and other clinical indicators, we have developed a precise model to predict the prognosis of patients with AEG (types II and III). The new prognostic nomogram could effectively enhance the predictive value of the TNM staging system. This scoring system can be advantageous and helpful for surgeons and patients.

Association of abnormal bowel health with major chronic diseases and risk of mortality.

PURPOSE: We aimed to explore the association of chronic constipation and diarrhea with major chronic diseases including cancer, cardiovascular disease (CVD), and diabetes, as well as with mortality risk. In addition, we characterized the interrelationship of inflammation with abnormal bowel health, major chronic diseases, and mortality. METHODS: Demographic characteristics, physical and laboratory examinations were collected from the National Health and Nutrition Examination Survey (NHANES) database 2005-2010. Chronic constipation or diarrhea was diagnosed by the shape and frequency of defecation. The number of samples used for the cancer, CVD, diabetes, and mortality analyses were 11,217, 11,168, 11,555, and 14,316, respectively. Logistic regression was used to analyze the association among abnormal bowel health, major chronic diseases, dietary inflammatory index (DII), and C-reactive protein (CRP). A Cox proportional hazard regression was performed to assess risk of all-cause mortality, and the Fine and Gray models were subsequently employed to calculate the cancer and CVD mortality risks. RESULTS: There were statistically positive associations of chronic diarrhea or constipation with breast and colon cancer, CVD, risks of all-cause mortality, and CVD mortality. Particularly in participants younger than 60, in addition to the positive correlations of chronic diarrhea with three major chronic diseases and all-cause mortality risk, chronic constipation also contributed to an elevated risk of CVD mortality. With respect to inflammation markers, an increased DII or CRP level was significantly associated with a higher prevalence of abnormal bowel health and major chronic diseases, and a higher mortality risk. CONCLUSIONS: Participants with abnormal bowel health were more likely linked to breast cancer, colon cancer, CVD, and risks of all-cause and CVD mortality. Moreover, inflammation may have a potential role in associations among abnormal bowel health, major chronic diseases and mortality. However, these findings need to be confirmed by further prospective studies.

Identification of Costimulatory Molecule-Related lncRNAs Associated With Gastric Carcinoma Progression: Evidence From Bioinformatics Analysis and Cell Experiments.

Costimulatory molecules (CMGs) play essential roles in multiple cancers. However, lncRNAs regulating costimulatory molecules have not been fully explored in gastric cancer (GC). Public data of GC patients were obtained from The Cancer Genome Atlas database. R software v4.1.1, SPSS v13.0, and GraphPad Prism 8 were used to perform all the analyses. The Limma package was used for differential expression analysis. The survival package was used for patient prognosis analysis. The gene set enrichment analysis (GSEA), gene ontology (GO), and the Kyoto encyclopedia of genes and genomes (KEGG) analysis were used for pathway enrichment analysis. qRT-PCR was used to detect the RNA level of target lncRNA. CCK-8 and colony formation assay were used to assess the proliferation ability of GC cells. The transwell assay was used to evaluate the invasion and migration ability of GC cells. We first identified CMG-related lncRNAs (CMLs) through co-expression analysis. Then, an eight-CML-based signature was constructed to predict patient overall survival (OS), which showed satisfactory predictive efficiency (the training cohort: 1-year AUC = 0.764, 3-year AUC = 0.810, 5-year AUC = 0.840; the validation cohort: 1-year AUC = 0.661, 3-year AUC = 0.718, 5-year AUC = 0.822). The patients in the high-risk group tend to have a worse prognosis. GSEA showed that epithelial-mesenchymal transition, KRAS signaling, and angiogenesis were aberrantly activated in high-risk patients. GO and KEGG analyses indicated that the biological difference between high- and low-risk patients was mainly enriched in the extracellular matrix. Immune infiltration analysis showed that macrophages (M1 and M2), dendritic cells, monocytes, Tregs, and T regulatory cells were positively correlated with the risk scores, partly responsible for the worsening OS of high-risk patients. Finally, lncRNA AP000695.2 was selected for further experiments. The result showed that AP000695.2 was upregulated in GC cell lines and could facilitate the proliferation, invasion, and migration of GC cells. In summary, this study established an effective prognosis model based on eight CMLs, which would be helpful for further therapy options for cancer. Also, we found that AP000695.2 could promote GC cell malignant phenotype, making it an underlying therapy target in GC.

Radiomic Signature Based on Dynamic Contrast-Enhanced MRI for Evaluation of Axillary Lymph Node Metastasis in Breast Cancer.

Background: To construct and validate a radiomic-based model for estimating axillary lymph node (ALN) metastasis in patients with breast cancer by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods: In this retrospective study, a radiomic-based model was established in a training cohort of 236 patients with breast cancer. Radiomic features were extracted from breast DCE-MRI scans. A method named the least absolute shrinkage and selection operator (LASSO) was applied to select radiomic features based on highly reproducible features. A radiomic signature was built by a support vector machine (SVM). Multivariate logistic regression analysis was adopted to establish a clinical characteristic-based model. The performance of models was analysed through discrimination ability and clinical benefits. Results: The radiomic signature comprised 6 features related to ALN metastasis and showed significant differences between the patients with ALN metastasis and without ALN metastasis (P < 0.001). The area under the curve (AUC) of the radiomic model was 0.990 and 0.858, respectively, in the training and validation sets. The clinical feature-based model, including MRI-reported status and palpability, performed slightly worse, with an AUC of 0.784 in the training cohort and 0.789 in the validation cohort. The radiomic signature was confirmed to provide more clinical benefits by decision curve analysis. Conclusions: The radiomic-based model developed in this study can successfully diagnose the status of lymph nodes in patients with breast cancer, which may reduce unnecessary invasive clinical operations.

Consumption of flavonoids and risk of hormone-related cancers: a systematic review and meta-analysis of observational studies.

BACKGROUND: Flavonoids seem to have hormone-like and anti-hormone properties so that the consumption of flavonoids may have potential effects on hormone-related cancers (HRCs), but the findings have been inconsistent so far. This meta-analysis was aimed to explore the association between flavonoids intake and HRCs risk among observational studies. METHODS: Qualified articles, published on PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) from January 1999 to March 2022 and focused on relationships between flavonoids (total, subclass of and individual flavonoids) and HRCs (breast, ovarian, endometrial, thyroid, prostate and testicular cancer), were retrieved for pooled analysis. Random effects models were performed to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Funnel plots and Begg's/Egger's test were used to evaluate the publication bias. Subgroup analyses and sensitivity analyses were conducted to explore the origins of heterogeneity. RESULTS: All included studies were rated as medium or high quality. Higher consumption of flavonols (OR = 0.85, 95% CI: 0.76-0.94), flavones (OR = 0.85, 95% CI: 0.77-0.95) and isoflavones (OR = 0.87, 95% CI: 0.82-0.92) was associated with a decreased risk of women-specific cancers (breast, ovarian and endometrial cancer), while the higher intake of total flavonoids was linked to a significantly elevated risk of prostate cancer (OR = 1.11, 95% CI: 1.02-1.21). A little evidence implied that thyroid cancer risk was augmented with the higher intake of flavones (OR = 1.24, 95% CI: 1.03-1.50) and flavanones (OR = 1.31, 95% CI: 1.09-1.57). CONCLUSIONS: The present study suggests evidence that intake of total flavonoids, flavonols, flavones, flavanones, flavan-3-ols and isoflavones would be associated with a lower or higher risk of HRCs, which perhaps provides guidance for diet guidelines to a certain extent. TRIAL REGISTRATION: This protocol has been registered on PROSPERO with registration number CRD42020200720 .