Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: Results from the European Prospective Investigation into Cancer and Nutrition study.

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73-1.23; Ptrend = .97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Prediagnostic Prescription Antibiotics Use and Survival in Patients with Colorectal Cancer: A Swedish National Register-Based Study.

BACKGROUND: Antibiotics use is associated with higher colorectal cancer risk, but little is known regarding any potential effects on survival. METHODS: We conducted a nationwide cohort study, using complete-population data from Swedish national registers between 2005 and 2020, to investigate prediagnostic prescription antibiotics use in relation to survival in colorectal cancer patients. RESULTS: We identified 36,061 stage I-III and 11,242 stage IV colorectal cancer cases diagnosed between 2010 and 2019. For stage I-III, any antibiotics use (binary yes/no variable) was not associated with overall or cancer-specific survival. Compared with no use, moderate antibiotics use (total 11-60 days) was associated with slightly better cancer-specific survival [adjusted HR (aHR) = 0.93; 95% confidence interval (CI), 0.86-0.99)], whereas very high use (>180 days) was associated with worse survival [overall survival (OS) aHR = 1.42; 95% CI, 1.26-1.60, cancer-specific survival aHR = 1.31; 95% CI, 1.10-1.55]. In analyses by different antibiotic types, although not statistically significant, worse survival outcomes were generally observed across several antibiotics, particularly macrolides and/or lincosamides. In stage IV colorectal cancer, inverse relationships between antibiotics use and survival were noted. CONCLUSIONS: Overall, our findings do not support any substantial detrimental effects of prediagnostic prescription antibiotics use on cancer-specific survival after colorectal cancer diagnosis, with the possible exception of very high use in stage I-III colorectal cancer. Further investigation is warranted to confirm and understand these results. IMPACT: Although the study findings require confirmation, physicians probably do not need to factor in prediagnostic prescription antibiotics use in prognosticating patients with colorectal cancer.

Impact of cumulative body mass index and cardiometabolic diseases on survival among patients with colorectal and breast cancer: a multi-centre cohort study.

BACKGROUND: Body mass index (BMI) and cardiometabolic comorbidities such as cardiovascular disease and type 2 diabetes have been studied as negative prognostic factors in cancer survival, but possible dependencies in the mechanisms underlying these associations remain largely unexplored. We analysed these associations in colorectal and breast cancer patients. METHODS: Based on repeated BMI assessments of cancer-free participants from four European countries in the European Prospective Investigation into Cancer and nutrition (EPIC) study, individual BMI-trajectories reflecting predicted mean BMI between ages 20 to 50 years were estimated using a growth curve model. Participants with incident colorectal or breast cancer after the age of 50 years were included in the survival analysis to study the prognostic effect of mean BMI and cardiometabolic diseases (CMD) prior to cancer. CMD were defined as one or more chronic conditions among stroke, myocardial infarction, and type 2 diabetes. Hazard ratios (HRs) and confidence intervals (CIs) of mean BMI and CMD were derived using multivariable-adjusted Cox proportional hazard regression for mean BMI and CMD separately and both exposures combined, in subgroups of localised and advanced disease. RESULTS: In the total cohort of 159,045 participants, there were 1,045 and 1,620 eligible patients of colorectal and breast cancer. In colorectal cancer patients, a higher BMI (by 1 kg/m2) was associated with a 6% increase in risk of death (95% CI of HR: 1.02-1.10). The HR for CMD was 1.25 (95% CI: 0.97-1.61). The associations for both exposures were stronger in patients with localised colorectal cancer. In breast cancer patients, a higher BMI was associated with a 4% increase in risk of death (95% CI: 1.00-1.08). CMDs were associated with a 46% increase in risk of death (95% CI: 1.01-2.09). The estimates and CIs for BMI remained similar after adjustment for CMD and vice versa. CONCLUSIONS: Our results suggest that cumulative exposure to higher BMI during early to mid-adulthood was associated with poorer survival in patients with breast and colorectal cancer, independent of CMD prior to cancer diagnosis. The association between a CMD diagnosis prior to cancer and survival in patients with breast and colorectal cancer was independent of BMI.

Antibiotics Use and Subsequent Risk of Colorectal Cancer: A Swedish Nationwide Population-Based Study.

BACKGROUND: Antibiotics use may increase colorectal cancer (CRC) risk by altering the gut microbiota, with suggestive evidence reported. Our study aims to investigate antibiotics use in relation to subsequent CRC risk. METHODS: This is a nationwide, population-based study with a matched case-control design (first primary CRC cases and 5 matched, cancer-free controls). Complete-population data, extracted from Swedish national registers for the period 2005-2016, were used to calculate odds ratios and 95% confidence intervals. RESULTS: We included 40 545 CRC cases and 202 720 controls. Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed. Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. We found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk. CONCLUSIONS: This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women. This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.

Keyhole Foraminotomy via a Percutaneous Posterior Full-endoscopic Approach for Cervical Radiculopathy: An Advanced Procedure and Clinical Study.

Endoscopic cervical foraminotomy is increasingly used for cervical spondylotic radiculopathy (CSR), but there is great concern about radiation exposure because of the heavy dependence of this surgical method on fluoroscopy. The objective of this study was to introduce in detail an advanced surgical technique of keyhole foraminotomy via a percutaneous posterior full-endoscopic approach as a treatment for CSR and investigate its clinical outcomes. We retrospectively reviewed 33 consecutive patients with CSR who underwent keyhole foraminotomy via a percutaneous posterior full-endoscopic approach from October 2015 to April 2017. The patients' general characteristics, including operative time, blood loss, hospital stay, complications, and recurrence, were obtained. Clinical outcomes were evaluated using the visual analogue scale (VAS) for radicular pain, the neck disability index (NDI) for functional assessment, and the modified MacNab criteria for patient satisfaction. All operations were successfully performed (mean operation time, 62 min), with no measurable blood loss or severe related complications. The mean follow-up was 25 months. The VAS and NDI scores were significantly improved as compared with those in the preoperative period (preoperative vs. final follow-up: 7.6±1.6 vs. 3.83±7.34 for VAS, P<0.01; 69.5%±10.5% vs. 17.54%±13.40% for NDI, P<0.01). Of the 33 patients, 32 (97.0%) had good-to-excellent global outcomes and all patients obtained symptomatic improvement. In conclusion, keyhole foraminotomy via a percutaneous posterior full-endoscopic approach is an efficient, safe, and feasible procedure for the treatment of CSR. Its simplified single-step blunt incision for localization appears to decrease radiation exposure risks.

Immediate Prone Positioning After Massive Gastric Aspiration Reduces Lung Injury Possibly by Attenuating Interleukin-6-Mediated Lung-Tissue Inflammation in Pigs.

Gastric aspiration, which can cause acute, diffuse, inflammatory lung injury, is of particular concern in critically ill patients. This study aimed to determine the effects of immediate prone positioning on the degree of lung injury and inflammatory response induced by gastric aspiration. Following induction of gastric aspiration by injection of gastric fluid, 16 healthy pigs were randomized to one of two groups: supine position (SP) or prone position (PP). After ventilation and monitoring for 6 hr, all pigs were euthanized. The ratio of the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FIO2) and the partial pressure of arterial carbon dioxide (PaCO2) were recorded during the 6-hr study period. Serum levels of interleukin (IL)-6 were measured every 2 hr, and the mean optical density (MOD) of IL-6 in lung tissues and lung-injury scores were measured at the end of the experiment. The PP group showed a significantly higher PaO2/FIO2 ratio, lower serum IL-6 concentration (p = .015), lower lung-injury scores (p = .012), and lower IL-6 concentration and MOD of IL-6 in lung tissue, especially in dorsal (p = .001, p = .021, respectively) and nondependent regions (p = .005, p = .035, respectively) than the SP group. There were no statistically significant differences in PaCO2 between the groups. Lung-injury severity was positively correlated with the IL-6 concentration and MOD of IL-6 in lung tissues (p < .05). These results suggest that immediate prone positioning alleviated the degree of aspiration-induced lung injury, possibly through mitigating IL-6-mediated lung inflammation.

Multi-functional self-assembled nanoparticles for pVEGF-shRNA loading and anti-tumor targeted therapy.

Although RNA interference (RNAi) technology shows great potential in cancer treatment, the tumor target delivery and sufficient cytosolic transport of RNAi agents are still the main obstacles for its clinical applications. Herein, we report a functional supramolecular self-assembled nanoparticle vector for RNAi agent loading and tumor target therapy. Molecular block adamantane-grafted poly(ethylene glycol) (Ad-PEG) was modified with epidermal growth factor receptor (EGFR)-specific binding ligand GE11 or pH-sensitive fusogenic peptide GALA and then used for self-assembly with cyclodextrin-grafted branched polyethylenimine (CD-PEI), adamantane-grafted polyamidoamine dendrimer (Ad-PAMAM), and plasmid DNA containing a small hairpin RNA expression cassette against vascular endothelial growth factor (VEGF) into functional DNA-loaded supramolecular nanoparticles (GE11&GALA-pshVEGF@SNPs) based on molecular recognition and charge interaction. These functional peptides facilitated the target cell binding, internalization, and endosomal escape of GE11&GALA-pshVEGF@SNPs, resulting in increased reporter gene expression and efficient targeted gene silencing. The systemic delivery of the GE11&GALA-pshVEGF@SNPs can efficiently downregulate the intratumoral VEGF protein levels, reduce blood vessel formation, and significantly inhibit A549 xenograft tumor growth. These results reveal the potential of these multifunctional self-assembled nanoparticles as a nucleic acid drug delivery system for the treatment of lung cancer.

[Preparation and Comparison of Arsenic Removal Granular Adsorbent Based on Iron-Manganese Sludge].

Backwashing sludge is an efficient adsorbent for arsenic removal. However, considering the practical application, it is unfavorable for solid-liquid separation. To overcome this disadvantage, a high-temperature baking method was used to prepare a granular adsorbent (GA) with iron-manganese sludge, along with an embedding method with drying (H-GA) and lyophilization (D-GA). The characterization results showed that the surface of the three adsorbents were rough, with specific surface areas of 43.830, 110.30, and 129.18 m2·g-1, respectively. The adsorption experiments showed that the adsorption of arsenic by H-GA and D-GA was much higher than that of GA. The maximum adsorption capacities of GA, H-GA, and D-GA were 5.05, 14.95, and 13.45 mg·g-1, respectively. The Langmuir model fit the adsorption process of arsenic by H-GA and D-GA better, whereas the Freundlich model fit the adsorption process of GA better. The Pseudo-first order model and Pseudo-second order model were suitable to describe the kinetic curves of the three adsorbents. The acidic environment was more conducive to the adsorption of arsenic. The particle adsorbents prepared by the embedding method, H-GA and D-GA, retained the original structure of iron-manganese sludge, and the specific surface area was much larger than that of GA; thus, the adsorption capacity was greater than that of GA. Drying and lyophilization had no significant effect on the adsorption performance of granular adsorbents prepared by embedding.

Change in Serum Level of Interleukin 6 and Delirium After Coronary Artery Bypass Graft.

BACKGROUND: Serum level of interleukin 6 (IL-6) is known to be associated with postoperative delirium. However, no consensus has emerged on the postoperative time point at which IL-6 level may predict postoperative delirium after coronary artery bypass graft surgery. OBJECTIVES: To compare trends in IL-6 levels in patients with and without postoperative delirium and to examine the relationship between IL-6 levels at different times and postoperative delirium after coronary artery bypass graft. METHODS: A prospective cohort study of patients who underwent their first elective isolated coronary artery bypass graft between November 2013 and August 2015 at a cardiac intensive care unit in Beijing, China. Concentrations of IL-6 were measured before the operation and at the 6th, 12th, and 18th postoperative hours. Participants were assessed for postoperative delirium twice daily for 5 days. Univariate and multivariate logistic regression analyses were done to determine associations between IL-6 levels at different time points, postoperative changes in IL-6 levels, and the occurrence of postoperative delirium. RESULTS: Postoperative delirium was diagnosed in 85 of 266 patients (32%). Levels of IL-6 were significantly higher in patients with postoperative delirium than in patients without it at the 6th, 12th, and 18th postoperative hours (P = .03, .004, and .001, respectively). Change in IL-6 level (odds ratio, 2.97; 95% CI, 1.20-7.31; P = .02) and IL-6 level of 583 pg/mL or higher at the 18th postoperative hour (odds ratio, 5.20; 95% CI, 1.84-14.70; P = .002) were associated with higher incidence of postoperative delirium. CONCLUSION: Interleukin 6 level (≥ 583 pg/mL) at the 18th postoperative hour may serve as a potent predictor of postoperative delirium in coronary artery bypass graft patients.

The protective effect and mechanism of rapamycin in the rat model of IgA nephropathy.

BACKGROUND: The pathogenesis of the development of IgA nephropathy has not been clear up to now. At present, some studies revealed that the mTOR pathway may participate in IgA nephropathy; however, the mechanism has not been systematically studied. In this study, we established an IgAN rat model to investigate the protective effects of rapamycin as a new type of immunosuppressant, as well as its therapeutic mechanisms. METHODS: After the establishment of IgA nephropathy model, rats were treated with different concentrations of rapamycin, and the protective effect of different concentrations of rapamycin on renal function of the rats was observed. The deposition of IgA was observed by immunofluorescence. The kidney expression of Akt and p70S6k proteins in mTOR pathway was examined using the western blot assay after rapamycin treatment. RESULTS: Morphology and immunofluorescence confirmed that the rat model of IgA nephropathy was successfully established. In particular, the level of proteinuria decreased with the increase of the dose of rapamycin, as well as the deposition of IgA in glomeruli. Moreover, the western blot analysis indicated that the expression of p70S6K in the downstream of mTOR pathway decreased and the upstream protein AKT of the mTOR pathway was overexpressed in the rats model. CONCLUSION: We found that rapamycin has protective effects in the IgA nephropathy rat model in a dose-dependent manner. In addition, the result of western blot assay suggested that rapamycin may display its therapeutic effects through interfering the AKT-mTOR-p70S6K signaling pathway.

[Start-up and Operation of Biofilter Coupled Nitrification and CANON for the Removal of Iron, Manganese and Ammonia Nitrogen].

A pilot-scale bio-filter coupled nitrification and CANON was started up to remove iron, manganese and ammonia nitrogen from groundwater in a plant, and the main removal route of ammonia nitrogen was analyzed. The experiment showed that the bio-filter could be started up successfully and achieved stable operation after 164 days of culture development. The value of △NH4+-N/△NO3--N was 1.49, and the oxidation and removal of Fe(Ⅱ), Mn(Ⅱ), and NH4+-N were (9.87±1.17), (2.25±0.06), and (1.51±0.06) mg·L-1, respectively. The calculation based on the quantitative relationship between nitrogen conservation and dissolved oxygen (DO) measurement indicated that the contribution of CANON to NH4+-N removal was 33.48%-38.87%, and the average ratio of ammonia nitrogen removal amount to DO was 1:3.79-1:3.94. The removal ratio of ammonia nitrogen was lower with lower temperature.

[Arsenic(â ¤) Removal by Granular Adsorbents Made from Backwashing Residuals from Biofilters for Iron and Manganese Removal].

Granular adsorbents for arsenic removal (GA) made from the backwashing residuals from iron and manganese removal biofilters for groundwater were characterized and examined as an arsenate sorbent. The GA were characterized by SEM-EDS microscopy, X-ray diffraction (XRD), and BET surface area measurement. The results showed that the GA had rough surfaces, developed pores, and were mainly amorphous, with small fractions of crystalline quartz and hematite. The surface area of the GA, which consists of many mesopores, was 43.8 m2·g-1. The kinetic studies revealed that arsenate adsorption on the GA was described by a pseudo-second-order kinetic equation, and the Freundlich isotherm equation fit the arsenate adsorption well (R2=0.994). The maximum adsorption capacity calculated by the Langmuir isotherm equation for As(Ⅴ) was 5.05 mg·g-1. Further studies showed that the GA operated well for As(Ⅴ) removal over a broad range in pH from 1.1 to 9.5. The coexistence of HCO3- and SO42- had no great influence on arsenic adsorption, while the H2PO4- and SiO32- showed negative effects. The GA can be regenerated well, and 82% of the original adsorption capacity was maintained after three regeneration cycles.

The quality of life of patients developed delirium after coronary artery bypass grafting is determined by cognitive function after discharge: A cross-sectional study.

AIMS: Postoperative delirium (POD) and declined cognitive function were common in patients (especially elderly patients) who underwent coronary artery bypass grafting (CABG), which may affect quality of life (QoL). The aim of this study was to determine the relationships among age, POD, declined cognitive function, and QoL in patients who underwent CABG. METHODS: Consecutive patients who underwent first time elective CABG and assessed for POD using Confusion Assessment Method for intensive care unit for 5 postoperative days from November 2013 to March 2015 were recruited. A cross-sectional study was conducted during April 2015 to assess their cognitive function and QoL, using the Telephone Interview for Cognitive Status Scale and Medical Outcomes Study 36-Item Short Form Health Survey. The relationships among age, POD, declined cognitive function, and QoL were tested using path analysis. RESULTS: Declined cognitive function was associated with poorer QoL. POD was associated with declined cognitive function but was not associated with poorer QoL. Ageing was not associated with QoL but was associated with POD and declined cognitive function. CONCLUSION: The QoL of patients developed delirium after CABG is determined by cognitive function after discharge. Necessary strategies should be implemented to prevent POD and declined cognitive function, especially in elderly patients.