Association between walking pace and risks of major chronic diseases in individuals with hypertension based on a prospective study in UK Biobank: Involvement of inflammation.

OBJECTIVE: Walking pace is associated with risks of major chronic diseases including cancer, cardiovascular disease (CVD) and diabetes mellitus type 2 (T2DM) in the general population. However, whether increasing walking pace could reduce risks of major chronic diseases in individuals with hypertension remains to be explored, and the underlying mechanism potentially mediated by low-grade inflammation is also unclear. METHODS: A total of 160,470 participants with hypertension were included based on the UK Biobank. The relationships of the walking pace and low-grade inflammation with risks of major chronic diseases in individuals with hypertension were assessed by the Cox proportional hazards model. Mediation analyses were performed to investigate the contribution of low-grade inflammation to the association between walking pace and risks of major chronic diseases. RESULTS: Individuals with hypertension at the brisk walking pace had decreased risks of overall cancer and site-specific cancers (liver, lung, and endometrial cancers), all CVD events (angina, atrial fibrillation, heart failure, myocardial infarction, peripheral vascular disease and stroke), and T2DM (hazard ratios: 0.42-0.91). Increasing low-grade inflammation was associated with higher risks of aforementioned diseases except liver cancer and atrial fibrillation. Furthermore, low-grade inflammation partially mediated associations of the walking pace with risks of lung cancer, T2DM, and all CVD events (except atrial fibrillation), with mediation proportion of 2.0%-9.8%. CONCLUSIONS: Brisk walking pace was linked to reduced risks of major chronic diseases in individuals with hypertension, partially mediated by low-grade inflammation. Improving walking pace may be beneficial for health in individuals with hypertension.

Efficacy and safety of trifluridine/tipiracil plus bevacizumab versus trifluridine/tipiracil monotherapy for refractory metastatic colorectal cancer: a retrospective cohort study.

Background: Several studies demonstrated trifluridine/tipiracil (TAS-102) plus bevacizumab (BEV) had better efficacy than the monotherapy of TAS-102 in refractory metastatic colorectal cancer (mCRC). However, it remains unclear whether Chinese population can benefit from this combination or not. Hence, we conducted this retrospective cohort study to compare the efficacy and safety between TAS-102 plus BEV with TAS-102 monotherapy in refractory mCRC. Methods: This retrospective cohort study enrolled patients (any age) with refractory mCRC from Hunan Cancer Hospital. The main inclusion criteria were histopathologically and/or radiographically confirmed refractory mCRC, World Health Organization (WHO) performance status of 0 to 2, adequate organ function, and initial treatment of TAS-102 with or without BEV between November 2020 and October 2022. Previous therapy with fruquintinib or regorafenib was allowed but not mandatory. Baseline demographic and clinical characteristics were collected appropriately. Every 2 or 3 treatment cycles, the patients were assessed by computed tomography (CT) scans and clinical assessments until disease progression or loss to follow-up. The National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 (NCI-CTCAE 5.0) were presented as n (%). The primary endpoint was investigator-evaluated overall survival (OS). As this is a retrospective cohort study, sample size calculation was not performed. Eligible patients would be enrolled as many as possible. Results: A total of 90 patients were enrolled, including 58 patients who received TAS-102 plus BEV and another 32 patients who received TAS-102 monotherapy. The known baseline characteristics were comparable (P<0.05). With a median follow-up of 4.60 months (range, 0.20-22.80), the median OS (mOS) time in the TAS-102 plus BEV group was longer than that in the TAS-102 monotherapy group (10.83 vs. 7.43 months), but the difference was not significant (P=0.79). The median progression-free survival (mPFS) time was comparable between the two groups (4.67 vs. 4.30 months, P=0.96). Multivariate Cox regression analysis demonstrated that undergoing therapy after TAS-102 either with or without BEV was an independent risk factor for OS [hazard ratio (HR) =0.25; 95% confidence interval (CI): 0.09-0.71, P<0.01], and previous treatment with cetuximab was an independent protective factor for PFS (HR =0.17; 95% CI: 0.03-0.91, P=0.04). Of the 70 patients who were evaluated, those receiving TAS-102 plus BEV showed trend of a higher objective response rate (ORR) and disease control rate (DCR) than those who received TAS-102 monotherapy (P=0.16 and P=0.29, respectively). Adverse events (AEs) were similar between the two groups, except that the incidence of platelet count decrease (grade ≥3) was significantly higher in the TAS-102 plus BEV group. Conclusions: There was a trend in favor of the combination of BEV plus TAS-102 regarding OS and DCR, without reaching statistical significance, and it means that there was no clear advantage of one over the other in terms of efficacy. Further prospective studies are still necessary to draw a definite conclusion.

Nomogram to predict overall survival of patients receiving radical gastrectomy and incomplete peri-operative adjuvant chemotherapy for stage II/III gastric cancer: a retrospective bi-center cohort study.

BACKGROUND: To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC). METHODS: The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system. RESULTS: A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (< 18.5 kg/m2), total gastrectomy, stage III disease and fewer cycles of PAC were identified to be independent predictors for poorer survival. The area under the curve (AUC) values of receiver operating characteristics (ROC) curve predicting 5-year survival probabilities and C-index were 0.768 and 0.742, 0.700 (95%CI: 0.674-0.726) and 0.689 (95%CI: 0.646-0.732) in the training and validation groups, respectively. The calibration curves in the validation cohort showed good agreement between the prediction and observation of 1-, 3- and 5-year survival probabilities. Furthermore, DCA showed that our model has a better net benefit than that of TNM staging system. CONCLUSIONS: The findings emphasize the value of completing PAC. The nomogram which was established to predict survival probability in patients with stage II/III GC receiving radical gastrectomy and incomplete PAC had good accuracy and was verified through both internal and external validation.

Joint association of biological aging and lifestyle with risks of cancer incidence and mortality: A cohort study in the UK Biobank.

BACKGROUND: Aging is a risk factor for cancer incidence and mortality. Biological aging can reflect the aging degree of the body better than chronological age and can be aggravated by unhealthy lifestyle factors. We aimed to assess the joint effect of biological aging and lifestyle with risks of cancer incidence and mortality. METHODS: This study included a total of 281,889 participants aged 37 to 73 from the UK Biobank database. Biological age was derived from chronological age and 9 clinical blood indicators, and lifestyle score was constructed by body mass index, smoking status, alcohol consumption, physical activity, and diet. Multivariate Cox hazard proportional regression model was used to analyze the independent and joint association of biological aging and lifestyle with risks of cancer incidence and mortality, respectively. RESULTS: Over a median follow-up period of 12.3 years, we found that older biological age was associated with increased risks of overall cancer, digestive system cancers, lung, breast and renal cancers incidence and mortality (HRs: 1.12-2.25). In the joint analysis of biological aging and lifestyle with risks of cancer incidence and mortality, compared with unhealthy lifestyle and younger biological age, individuals with healthy lifestyle and older biological age had decreased risks of incidence (8% âˆ¼ 60%) and mortality (20% âˆ¼ 63%) for overall, esophageal, colorectal, pancreatic and lung cancers. CONCLUSIONS: Biological aging may be an important risk factor for cancer morbidity and mortality. A healthier lifestyle is more likely to mitigate the adverse effects of biological aging on overall cancer and some site-specific cancers.

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.

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.

Prognostic value of post-operative serum procalcitonin in gastric adenocarcinoma patients undergoing radical gastrectomy: propensity score matching analysis of extended cohort from a prospective bi-center study.

BACKGROUND: The aim of this study was to investigate the predictive value of procalcitonin (PCT) on post-operative day (POD) 3 and 5 for the prognosis of gastric adenocarcinoma (GA) patients who underwent radical gastrectomy surgery in extended cohort from a prospective bi-center study. METHODS: Consecutive GA patients who received surgery in the Hunan Cancer Hospital were enrolled as the training cohort, and those from Wuhan Union Hospital were included as external validation cohort. The optimal cutoff concentration of PCT for overall survival (OS) in the training cohort was determined by X-tile. The independent predictive factors for OS were identified using univariate and multivariate Cox regression analyses. Furthermore, the predictive value of elevated PCT was clarified in the validation cohort and propensity score matched cohort, respectively. RESULTS: The optimal cutoff concentrations of PCT for OS were 0.67 ng/mL at POD 3 and 0.39 ng/mL at POD 5 in the training cohort (n = 906). Patients with higher PCT concentrations (≥ 0.39 ng/mL) at POD 5 had a significantly worse prognosis whether developing post-operative infections or not. Moreover, a synergistic influence was confirmed in those with elevated PCT concentration and infections. Multivariate analyses confirmed that PCT concentration ≥ 0.39 ng/mL at POD 5 was significantly associated with poorer survival in training cohort (HR: 1.422, 95% CI 1.041-1.943, P = 0.027), validation cohort (n = 297, HR: 2.136, 95% CI 1.073-4.252, P = 0.031) and matched cohort (n = 901, HR: 1.454, 95% CI 1.104-1.914, P = 0.008), separately. CONCLUSIONS: PCT concentration ≥ 0.39 ng/mL at POD 5 was a reliable predictor for poorer prognosis in GA patients undergoing radical gastrectomy.

Surgical resection for second primary colorectal cancer: a population-based study.

Background: Second primary colorectal cancer (CRC) is attributed to a crucial component of the CRC population. Still, its treatments remain unclear due to the troublesome conditions originating from multiple primary cancers and the lack of quality evidence. This study aimed to determine that which type of surgical resection is the eligible treatment for second primary CRC among patients with a prior cancer history. Methods: This cohort study retrospectively collected patients with second primary stage 0-III CRC in the Surveillance, Epidemiology, and End Results database from 2000 to 2017. Prevalence of surgical resection in second primary CRC, overall survival (OS) and disease-specific survival (DSS) of patients who received different surgical interventions were estimated. Results: A total of 38,669 patients with second primary CRC were identified. Most of the patients (93.2%) underwent surgical resection as initial treatment. Approximately 39.2% of the second primary CRCs (N = 15,139) were removed with segmental resection, while 54.0% (N = 20,884) were removed through radical colectomy/proctectomy. Surgical resection was associated with a significantly favorable OS and DSS compared to those not receiving any surgical operations for second primary CRC [OS: adjusted Hazard ratios (adjusted HR): 0.35; 95% CI: 0.34-0.37, p < 0.001; DSS: adjusted HR: 0.27; 95% CI: 0.25-0.29, p < 0.001]. Segmental resection considerably outperformed radical resection in terms of OS and DSS (OS: adjusted HR: 0.97; 95% CI: 0.91-1.00, p = 0.07; DSS: adjusted HR: 0.92; 95% CI: 0.87-0.97, p = 0.002). Segmental resection was also associated with a significantly reduced cumulative mortality of postoperative non-cancer comorbidities. Conclusion: Surgical resection demonstrated excellent oncological superiority for second primary CRC and was used to remove the vast majority of second primary CRCs. In comparison to radical resection, segmental resection offered a better prognosis and reduced postoperative non-cancer complications. The second primary colorectal cancers should be resected if the patients can afford surgical operations.

Unhealthy lifestyles and clusters status among 3637 adolescents aged 11-23 years: a school-based cross-sectional study in China.

BACKGROUND: Unhealthy lifestyles are risk factors for non-communicable diseases (NCDs) and tend to be clustered, with a trajectory that extends from adolescence to adulthood. This study investigated the association of diets, tobacco, alcohol, physical activity (PA), screen time (ST) and sleep duration (SD) in a total of six lifestyles, separately and as cumulative lifestyle scores, with sociodemographic characteristics among school-aged adolescents in the Chinese city of Zhengzhou. METHODS: In the aggregate, 3,637 adolescents aged 11-23 years were included in the study. The questionnaire collected data on socio-demographic characteristics and lifestyles. Healthy and unhealthy lifestyles were identified and scored, depending on the individual score (0 and 1 for healthy and unhealthy lifestyles respectively), with a total score between 0 and 6. Based on the sum of the dichotomous scores, the number of unhealthy lifestyles was calculated and divided into three clusters (0-1, 2-3, 4-6). Chi-square test was used to analyze the group difference of lifestyles and demographic characteristics, and multivariate logistic regression was used to explore the associations between demographic characteristics and the clustering status of unhealthy lifestyles. RESULTS: Among all participants, the prevalence of unhealthy lifestyles was: 86.4% for diet, 14.5% for alcohol, 6.0% for tobacco, 72.2% for PA, 42.3% for ST and 63.9% for SD. Students who were in university, female, lived in country (OR = 1.725, 95% CI: 1.241-2.398), had low number of close friends (1-2: OR = 2.110, 95% CI: 1.428-3.117; 3-5: OR = 1.601, 95% CI: 1.168-2.195), and had moderate family income (OR = 1.771, 95% CI: 1.208-2.596) were more likely to develop unhealthy lifestyles. In total, unhealthy lifestyles remain highly prevalent among Chinese adolescents. CONCLUSION: In the future, the establishment of an effective public health policy may improve the lifestyle profile of adolescents. Based on the lifestyle characteristics of different populations reported in our findings, lifestyle optimization can be more efficiently integrated into the daily lives of adolescents. Moreover, it is essential to conduct well-designed prospective studies on adolescents.

Correlation analysis of the expression of mesenchymal circulating tumor cells and CD133 with the prognosis of colorectal cancer.

OBJECTIVE: To evaluate the expression of tumor stem cell marker CD133 in peripheral blood circulating tumor cells (CTC) and the value of CD133 in prognosis of patients with colorectal cancer (CRC). METHODS: Preoperative/pre-chemotherapy peripheral blood samples of 63 patients with CRC from January 2016 to January 2021 were selected to detect peripheral blood CTC by CanPatrol CTC enrichment technology. Expression of CD133 in different epithelial-mesenchymal transition (EMT) typing CTC was analyzed. Clinical data (including tumor size, tumor stage, pathological typing, molecular typing, lymph node metastasis, distant metastasis, carcinoembryonic antigen (CEA), and CA-199 expression), PFS time and OS time were followed up. The expression of CD133 in different CTCs was compared, and the correlation between CD133 and patient survival time was compared. RESULTS: The positive rate of E-CTC in patients with tumor diameter ≥5 cm was significantly higher than that of patients with tumor diameter <5 cm (P=0.035). The positive rate of M-CTC in patients with diabetes was significantly higher than that of patients without diabetes (P=0.006). The CD133-positive M-CTCs were significantly higher in DM and CEA>5 ng/mL patients than in non-DM and CEA≤5 ng/mL patients (P<0.001, P=0.0195). Fifty-five patients were followed up for a median of 14 months. During follow-up, 19 had disease progression and five died. According to the cutoff point obtained by ROC analysis, the PFS of M-CTC>2.5/5 ml patients (0%) was lower than that of ≤2.5/5 ml patients (76.5%), P<0.05. PFS in patients with CD133-positive M-CTC>0.5/5 mL (18.6%) was lower than in patients with ≤0.5/5 ml (76.5%), P<0.05. However, thedifference in the OS between patients with CD133-positive M-CTC>0.5/5 ml (71.7%) and those with ≤0.5/5 ml (93.8%), was not significant, P=0.054. CONCLUSION: CD133 positive M-CTC is closely related to distant metastasis in CRC. The expression of CD133 in CTC, especially in M-CTC, can be used as a prognostic indicator for colorectal cancer.

A two-step lighting DNA tetrahedral nanoprobe for precise imaging-guided photodynamic therapy of tumors.

Herein, we innovatively propose a mucin 1 and azoreductase dual-responsive DNA tetrahedral nanoprobe for two-step lighting imaging-guided photodynamic therapy of tumors. We hope that this highly specific, responsive and well biocompatible drug delivery system can be effectively used for the performance of cancer therapy in the hypoxia-related biomedical field.

Effect of tumor exosome-derived Lnc RNA HOTAIR on the growth and metastasis of gastric cancer.

PURPOSE: HOX transcribed antisense RNA (HOTAIR) is a long noncoding RNA (LncRNA) that promotes tumor progression. Exosomes are critically involved in cancer progression. The presence of HOTAIR in the circulating exosomes and the roles of exosomal HOTAIR in gastric cancer (GC) remains unknown. This study aimed to investigate the role of HOTAIR in exosomes in promoting the growth and metastasis of GC. METHODS: Serum exosomes from GC patients were captured by CD63 immunoliposome magnetic spheres (CD63-IMS), and the biological characteristics of the exosomes were identified. The expression levels of HOTAIR in GC cells, tissues, serum and serum exosomes were detected by fluorescence quantitative PCR (qRT-PCR), and the clinicopathological correlation was statistically analyzed. The growth and metastasis abilities of GC cells with HOTAIR knockdown in vitro were evaluated by cell experiment. The effects of HOTAIR highly-expressed NCI-N87 cell-derived exosomes were used to treat HOTAIR lowly-expressed MKN45 cells on GC growth and metastasis were also evaluated. RESULTS: The exosomes isolated by CD63-IMS had a particle size of 89.78 ± 4.8 nm and were oval membranous particles. The expression of HOTAIR in tumor tissues and serum of GC patients was increased (P < 0.05), and the expression of HOTAIR in serum exosomes was significantly increased (P < 0.01). The in NCI-N87 and MKN45 cell experiment demonstrated that HOTAIR knockdown by RNA interference suppressed cell growth and metastasis in NCI-N87 cells. Coculture of exosomes secreted by NCI-N87 cells with MKN45 cells significantly increased the expression of HOTAIR, and enhanced cell growth and metastasis. CONCLUSION: LncRNA HOTAIR can be used as a potential biomarker which provides a new way for the diagnosis and treatment of GC.

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.

The association of blood ctDNA levels to mutations of marker genes in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a deadly and commonly diagnosed cancer. Cell-free circulating tumor DNAs (ctDNA) have been used in the diagnosis and treatment of CRC, but there are open questions about the relationship between ctDNAs and CRC. Although mutations of genes detected by ctDNA in CRC have been studied, the quantitative relationship between ctDNA mutations and ctDNA concentration has not been addressed. AIMS: We hypothesized that there was an association between mutations of genes identified in ctDNAs and ctDNA concentration. His study examined this association in a population of CRC patients. METHODS: In 85 CRC patients, we sampled 282 mutations in 36 genes and conducted an association study based on a Random forest model between mutations and ctDNA concentrations in all patients. RESULTS: This association study showed that mutations on five genes, ALK, PMS2, KDR, MAP2K1, and MSH2, were associated with the ctDNA concentrations in CRC patients' blood samples. Because ctDNA mutations correlate with ctDNA level, we can infer the tumor burden or tumor size from ctDNA mutations, as well as the survival time for prognosis. CONCLUSION: Our findings shed light on the associations between mutations of genes identified in ctDNAs and ctDNA concentration in the blood of CRC patients. This discovery provides information regarding the tumor burden or tumor size based on ctDNA mutations.

F-Box Protein 43, Stabilized by N6-Methyladenosine Methylation, Enhances Hepatocellular Carcinoma Cell Growth and Invasion via Promoting p53 Degradation in a Ubiquitin Conjugating Enzyme E2 C-Dependent Manner.

The roles of F-box protein 43 (FBXO43) in carcinogenesis have been rarely revealed. The present study investigates the expression, function, and underlying mechanism of FBXO43 in hepatocellular carcinoma (HCC). Firstly, the expression and clinical significance of FBXO43 in HCC were investigated bioinformatically and experimentally using online omics data and local tissue samples. The role of N6-methyladenosine modification (m6A) of mRNA in regulating FBXO43 expression and the effects of m6A/FBXO43 axis alteration on cell proliferation and invasion were investigated further. Moreover, the underlying mechanism of the oncogenic FBXO43 was also explored. The results demonstrated that FBXO43 was significantly upregulated in HCC and was positively correlated with advanced progression and poor prognosis in patients. METTL3 and IGF2BP2 expressions were positively correlated with FBXO43 expression and served as the writer and reader of FBXO43 m6A, respectively, which stabilized and upregulated FBXO43 mRNA in HCC. FBXO43 silencing significantly reduced cell proliferation and invasion, and ectopic expression of FBXO43 could significantly restore the inhibitory effects caused by METTL3 and IGF2BP2 depletion in HCC cells. Mechanistically, FBXO43 depletion reduced the expression of UBE2C, a p53 ubiquitin-conjugating enzyme, suppressed proteasomal degradation of p53, and thus inhibited cell proliferation and invasion in HCC. In summary, the present study revealed that METTL3/IGF2BP2 mediated m6A contributed to the upregulation of FBXO43 that promoted the malignant progression of HCC by stimulating p53 degradation in a UBE2C-dependent manner, highlighting the promising application of FBXO43 as a target in HCC treatment.

Classification of precancerous lesions based on fusion of multiple hierarchical features.

PURPOSE: To investigate an identification method for precancerous gastric cancer based on the fusion of superficial features and deep features of gastroscopic images. The purpose of this study is to make most use of superficial features and deep features to provide clinicians with clinical decision support to assist the diagnosis of precancerous gastric diseases and reduce the workload of doctors. METHODS: According to the nature of gastroscopic images, 75-dimensional shallow features were manually designed, including histogram features, texture features and high-order features of the image; then, based on the constructed convolutional neural networks such as ResNet and GoogLeNet, before the output layer. A fully connected layer is added as the deep feature of the image. In order to ensure consistent feature weights, the number of neurons in the fully connected layer is designed to be 75 dimensions. Therefore, the superficial and deep features of the image are concatenated, and a machine learning classifier is used to identify gastric polyps, there are three types of gastric precancerous diseases such as gastric polyps, gastric ulcers and gastric erosions. RESULTS: A dataset with 420 images was collected for each disease, and divided into a training set and a test set with a ratio of 5:1, and then based on the dataset, three methods, such as traditional machine learning, deep learning, and feature fusion, were used respectively. For model training and testing of traditional machine learning and feature fusion, SVM, RF and BP neural network are used as the classification results of the classifier. For deep learning, the GoogLeNet, ResNet, and ResNeXt were implemented. The test results of the model on the test set show that the recognition accuracy of the proposed feature fusion method reaches (SVM: 85.18%; RF: 83.42%; BPNN: 85.18%), which is better than the traditional machine learning method (SVM: 80.17%; RF: 82.37%; BPNN: 84.12%) and the deep learning method (GoogLeNet: 82.54%; ResNet-18: 81.67%; ResNet-50: 81.67%; ResNeXt-50: 82.11%), which proves that this method has obvious advantages. CONCLUSION: This study provides a new strategy for the identification of precancerous gastric cancer, improving the efficiency and accuracy of precancerous gastric cancer identification, and hopes to provide substantial practical help for the identification of gastric precancerous diseases.

Efficacy, safety, and predictors of fruquintinib plus anti-programmed death receptor-1 (PD-1) antibody in refractory microsatellite stable metastatic colorectal cancer in a real-world setting: a retrospective cohort study.

Background: Patients with microsatellite stable (MSS) advanced colorectal cancer (CRC) have few alternatives for salvage therapy and a large unmet clinical need. Preclinical studies demonstrate that fruquintinib combined with anti-programmed death protein 1 (PD-1) has a synergistic anti-tumor effect. But a few phase 2 clinical studies show inconsistent efficacy of this combination therapy in CRC. The aim of this study was to investigate the efficacy, safety, and predictors of fruquintinib plus PD-1 antibodies in refractory MSS metastatic CRC (mCRC) in a real-world setting. Methods: We performed a retrospective single-center analysis to assess the outcomes of patients with MSS mCRC who were treated with fruquintinib plus anti-PD-1 antibodies subsequent to the failure of standard therapies at the Hunan Cancer Hospital. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were reviewed and evaluated. The primary endpoint was OS. The impact on OS and PFS was examined using the Cox regression model. Results: Between 1 January 2019 and 30 June 2022, we enrolled 70 eligible patients. The median follow-up was 17.2 months (range, 5.3-32.9 months). The median OS (mOS) and median PFS (mPFS) were 19.48 and 5.5 months respectively. The ORR was 11.43% and the DCR was 84.29%. Multivariate Cox regression analysis reveals liver metastasis (LM) without local treatment was a risk factor for OS [hazard ratio (HR) =5.31, P=0.0184], whereas that with local treatment (HR =2.19, P=0.263) was not. The most common adverse events were hand-foot syndrome (37.14%), hypertension (34.29%), mucositis oral (32.86%). No serious adverse effects or adverse effect-related deaths were reported. There were no instances of severe adverse effects or deaths related to adverse effects reported. Conclusions: Our study indicates that the combination of fruquintinib and anti-PD-1 antibodies can improve the OS and PFS with a tolerable toxicity profile for Chinese patients with refractory MSS mCRC. LM without local therapy is a negative prognostic factor for OS, but those with local treatment can significantly prolong survival. We require additional well-structured, prospective, and extensive studies to confirm and validate these findings.

Clinical Value of PET.CT Based on Big Data in Colorectal and Peritoneal Metastatic Cancer.

This study focuses on the evaluation of the clinical utility of PET-CT imaging in peritoneal metastases and colorectal cancer. One hundred patients with colorectal peritoneal metastases, who underwent whole-body PET-CT imaging from January 2015 to December 2019, were selected as the experimental group, and 20 healthy individuals were selected as the control group. The SUVmax of the two groups of patients was 5.73 ± 3.84 and 2.70 ± 2.32, respectively, and the difference was statistically significant. The SUVmax AUC was 0.720, and the AUC of serum AFP, CEA, CA125, and CA199 were 0.596, 0.677, 0.642, and 0.696, respectively. Conclusion. 100 patients with colorectal and peritoneal metastatic cancer underwent PET/CT examination. The follow-up or other imaging examinations confirmed the diagnosis. Analysis of the ROC curve in this study found that with a peritoneal SUVmax> 3.2 as the diagnostic index for colorectal peritoneal metastatic cancer, the sum of sensitivity and specificity reached the maximum.