Harnessing eCIRP by PS-OMe miR130: A promising shield against hemorrhage-induced lung injury.

INTRODUCTION: Hemorrhagic shock (HS) poses a life-threatening condition with the lungs being one of the most susceptible organs to its deleterious effects. Extracellular cold-inducible RNA binding protein (eCIRP) has emerged as a pivotal mediator of inflammation, and its release has been observed as a case of HS-induced tissue injury. Previous studies unveiled a promising engineered microRNA, designated PS-OMe miR130, which inhibits eCIRP, thereby safeguarding vital organs. In this study, we hypothesized that PS-OMe miR130 serves as a protective shield against HS-induced lung injury by curtailing the overzealous inflammatory immune response. METHODS: Hemorrhagic shock was induced in male C57BL6 mice by withdrawing blood via a femoral artery cannula to a mean arterial pressure of 30 mm Hg for 90 min. The mice were resuscitated with twice the shed blood volume with Ringer's Lactate solution. They were then treated intravenously with either PBS (vehicle) or 62.5 nmol PS-OMe miR130. At 4 h later, blood and lungs were harvested. RESULTS: Following PS-OMe miR130 treatment in HS mice, a substantial decrease was observed in serum injury markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and blood urea nitrogen (BUN). Serum IL-6 exhibited a similar reduction. In lung tissues, PS-OMe miR130 led to a significant decrease in the mRNA expressions of pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α), chemokines (KC and MIP-2), and an endothelial injury marker, E-selectin. PS-OMe miR130 also produced substantial inhibition of lung MPO activity and resulted in a marked reduction in lung injury as evidenced by histological evaluation. This was further confirmed by the observation that PS-OMe miR130 significantly reduced the presence of Ly6G-positive neutrophils and TUNEL-positive apoptotic cells. CONCLUSION: PS-OMe miR130 emerges as a potent safeguard against HS-induced lung injury by effectively inhibiting proinflammation and injuries, offering a promising therapeutic strategy in such critical clinical condition.

Metabolomic landscape of overall and common cancers in the UK Biobank: A prospective cohort study.

Information about the NMR metabolomics landscape of overall, and common cancers is still limited. Based on a cohort of 83,290 participants from the UK Biobank, we used multivariate Cox regression to assess the associations between each of the 168 metabolites with the risks of overall cancer and 20 specific types of cancer. Then, we applied LASSO to identify important metabolites for overall cancer risk and obtained their associations using multivariate cox regression. We further conducted mediation analysis to evaluate the mediated role of metabolites in the effects of traditional factors on overall cancer risk. Finally, we included the 13 identified metabolites as predictors in prediction models, and compared the accuracies of our traditional models. We found that there were commonalities among the metabolic profiles of overall and specific types of cancer: the top 20 frequently identified metabolites for 20 specific types of cancer were all associated with overall cancer; most of the specific types of cancer had common identified metabolites. Meanwhile, the associations between the same metabolite with different types of cancer can vary based on the site of origin. We identified 13 metabolic biomarkers associated with overall cancer, and found that they mediated the effects of traditional factors. The accuracies of prediction models improved when we added 13 identified metabolites in models. This study is helpful to understand the metabolic mechanisms of overall and a wide range of cancers, and our results also indicate that NMR metabolites are potential biomarkers in cancer diagnosis and prevention.

A NOVEL OLIGONUCLEOTIDE MRNA MIMIC ATTENUATES HEMORRHAGE-INDUCED ACUTE LUNG INJURY.

ABSTRACT: Hemorrhagic shock (HS) is accompanied by a pronounced activation of the inflammatory response in which acute lung injury (ALI) is one of the most frequent consequences. Among the pivotal orchestrators of this inflammatory cascade, extracellular cold-inducible RNA-binding protein (eCIRP) emerges as a noteworthy focal point, rendering it as a promising target for the management of inflammation and tissue injury. Recently, we have reported that oligonucleotide poly(A) mRNA mimic termed A 12 selectively binds to the RNA binding region of eCIRP and inhibits eCIRP binding to its receptor TLR4. Furthermore, in vivo administration of eCIRP induces lung injury in healthy mice and that mouse deficient in CIRP showed protection from inflammation-associated lung injury. We hypothesize that A 12 inhibits systemic inflammation and ALI in HS. To test the impacts of A 12 on systemic and lung inflammation, extent of inflammatory cellular infiltration and resultant lung damage were evaluated in a mouse model of HS. Male mice were subjected to controlled hemorrhage with a mean arterial pressure of 30 mm Hg for 90 min and then resuscitated with Ringer's lactate solution containing phosphate-buffered saline (vehicle) or A 12 at a dose of 4 nmol/g body weight (treatment). The infusion volume was twice that of the shed blood. At 4 h after resuscitation, mice were euthanized, and blood and lung tissues were harvested. Blood and tissue markers of inflammation and injury were evaluated. Serum markers of injury (lactate dehydrogenase, alanine transaminase, and blood urea nitrogen) and inflammation (TNF-α, IL-6) were increased after HS and A 12 treatment significantly decreased their levels. A 12 treatment also decreased lung levels of TNF-α, MIP-2, and KC mRNA expressions. Lung histological injury score, neutrophil infiltration (Ly6G staining and myeloperoxidase activity), and lung apoptosis were significantly attenuated after A 12 treatment. Our study suggests that the capacity of A 12 in attenuating HS-induced ALI and may provide novel perspectives in developing efficacious pharmaceutics for improving hemorrhage prognosis.

Effect of trace element mixtures on the outcome of patients with esophageal squamous cell carcinoma: a prospective cohort study in Fujian, China.

BACKGROUND: The evidence about the effects of trace elements on overall survival(OS) of patients with esophageal squamous cell carcinoma(ESCC) is limited. This study aims to evaluate mixed effects of plasma trace elements on OS of ESCC. METHODS: This prospective cohort analysis included 497 ESCC patients with a median follow-up of 52.3 months. The concentrations of 17 trace elements were measured. We fitted Cox's proportional hazards regression, factor analysis and Bayesian kernel machine regression (BKMR) models to estimate the association between trace elements and OS. RESULTS: Our analysis found that in the single-element model, Co, Ni, and Cd were associated with an increased risk of death, while Ga, Rb, and Ba were associated with a decreased risk. Cd had the strongest risk effect among all elements. As many elements were found to be mutually correlated, we conducted a factor analysis to identify common factors and investigate their associations with survival time. The factor analysis indicated that the factor with high factor loadings in Ga, Ba and B was linked to a decreased risk of death, while the factor with high factor loadings in Co, Ti, Cd and Pb was associated with a borderline significantly increased risk. Using BKMR analysis to disentangle the interaction between elements in significant factors, we discovered that Ga interacted with Ba and both elements had U-shaped effects with OS. Cd, on the other hand, had no interaction with other elements and independently increased the risk of death. CONCLUSIONS: Our analysis revealed that Ga, Ba and Cd were associated with ESCC outcome, with Ga and Ba demonstrating an interaction. These findings provide new insights into the impact of trace elements on the survival of patients with ESCC.

Association of food intake with a risk of metabolic dysfunction-associated fatty liver disease: a cross-sectional study.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common liver disease, the risk of which can be increased by poor diet. The objective of this study was to evaluate the associations between food items and MAFLD, and to propose reasonable dietary recommendations for the prevention of MAFLD. Methods: Physical examination data were collected from April 2015 through August 2017 at Nanping First Hospital (n = 3,563). Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. The association between food intake and the risk of MAFLD was assessed by using the inverse probability weighted propensity score. Results: Beverages (soft drinks and sugar-sweetened beverages) and instant noodles were positively associated with MAFLD risk, adjusting for smoking, drinking, tea intake, and weekly hours of physical activity [adjusted odds ratio (ORadjusted): 1.568; P = 0.044; ORadjusted: 4.363; P = 0.001]. Milk, tubers, and vegetables were negatively associated with MAFLD risk (ORadjusted: 0.912; P = 0.002; ORadjusted: 0.633; P = 0.007; ORadjusted: 0.962; P = 0.028). In subgroup analysis, the results showed that women [odds ratio (OR): 0.341, 95% confidence interval (CI): 0.172-0.676] had a significantly lower risk of MAFLD through consuming more tubers than men (OR: 0.732, 95% CI: 0.564-0.951). Conclusions: These findings suggest that reducing consumption of beverages (soft drinks and sugar-sweetened beverages) and instant noodles, and consuming more milk, vegetables, and tubers may reduce the risk of MAFLD.

ER translocon inhibitor ipomoeassin F inhibits triple-negative breast cancer growth via blocking ER molecular chaperones.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer where no effective therapy has been developed. Here, we report that the natural product ER translocon inhibitor ipomoeassin F is a selective inhibitor of TNBC cell growth. A proteomic analysis of TNBC cells revealed that ipomoeassin F significantly reduced the levels of ER molecular chaperones, including PDIA6 and PDIA4, and induced ER stress, unfolded protein response (UPR) and autophagy in TNBC cells. Mechanistically, ipomoeassin F, as an inhibitor of Sec61α-containing ER translocon, blocks ER translocation of PDIA6, inducing its proteasomal degradation. Silencing of PDIA6 or PDIA4 by RNA interferences or treatment with a small molecule inhibitor of the protein disulfide isomerases in TNBC cells successfully recapitulated the ipomoeassin F phenotypes, including the induction of ER stress, UPR and autophagy, suggesting that the reduction of PDIAs is the key mediator of the pharmacological effects of ipomoeassin F. Moreover, ipomoeassin F significantly suppressed TNBC growth in a mouse tumor xenograft model, with a marked reduction in PDIA6 and PDIA4 levels in the tumor samples. Our study demonstrates that Sec61α-containing ER translocon and PDIAs are potential drug targets for TNBC and suggests that ipomoeassin F could serve as a lead for developing ER translocon-targeted therapy for TNBC.

Association between the Preoperative Dietary Antioxidant Index and Postoperative Quality of Life in Patients with Esophageal Squamous Cell Carcinoma: A Prospective Study Based on the TTD Model.

OBJECTIVE: Dietary antioxidants are associated with risk of death in cancer patients, and they were used to evaluate the prognosis of cancer patients. Dietary antioxidant index (DAI) can be used to evaluate dietary antioxidant content comprehensively; this study aimed to investigate the effect of preoperative DAI on health-related quality of life in patients with esophageal cell squamous carcinoma (ESCC). METHODS: Data on dietary intakes were collected using a validated food-frequency questionnaire (FFQ). DAI was calculated for all study participants based on FFQ data of each participant. The study involved conducting several follow-up activities with patients diagnosed with ESCC to evaluate their quality of life. The approach employed in the study was to conduct a telephone interview. The EORTC Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30, version 3.0) and the Esophageal Cancer Module (EORTC QLQ-OES18) were used to collect data on the quality of life of the patients; all patients completed the full follow-up. RESULTS: This prospective study was performed on 376 participants who were recruited from Fujian Cancer Hospital and First Hospital of Fujian Medical University. They all were diagnosed with ESCC. The results indicated that the time to deterioration of global health status (p = 0.043), cognitive functioning (p = 0.031), dry mouth (p = 0.019), and speech problems (p = 0.031) significantly delay in the high DAI group. Univariate and multivariate Cox regression analysis showed that global health status (HR = 0.718, 95% CI: 0.532-0.969), cognitive functioning (HR = 0.641, 95% CI: 0.450-0.913), dry mouth (HR = 0.637, 95% CI: 0.445-0.911), and speech problems (HR = 0.651, 95% CI: 0.449-0.945) were improved in the high DAI group. CONCLUSIONS: Prognostic value of preoperative DAI was significant for patients with ESCC who undergo surgical intervention. Its level was positively correlated with the postoperative quality of life of patients, which can delay and improve the occurrence of postoperative physical function and symptom deterioration.

Determinants of gastric cancer screening attendance in Southeastern China: a cross-sectional study.

OBJECTIVES: This study aimed to identify the determinants of gastric cancer screening attendance among individuals aged 40 years in a region with high gastric cancer in China. DESIGN: An anonymous, cross-sectional survey was conducted between October 2021 and March 2022. SETTING: A self-administered online survey was conducted in Fujian Province in Southeastern China. PARTICIPANTS: People aged 40 years living in five selected cities in Fujian Province with no history of cancer. MAIN OUTCOME MEASURES: Gastric cancer screening attendance was measured with the question 'Have you ever been screened for gastric cancer in the past'. RESULTS: In total, 2547 complete responses were obtained. The mean age of respondents was 47.72±7.20 years, and 59.8% were men. A total of 42.6% of participants reported that they had undergone gastric cancer screening. The result of multivariable logistic regression analysis showed that participants with a first-degree relative affected with gastric cancer (OR=2.02, 95% CI: 1.58 to 2.59) and high perceived susceptibility of gastric cancer (OR=2.03, 95% CI: 1.58 to 2.59) were the strongest facilitators for screening attendance. Other factors positively associated with screening attendance were age 51-60 years (OR=1.69, 95% CI: 1.31 to 2.18), living in urban regions (OR=1.27, 95% CI: 1.05 to 1.55), friends/neighbours/colleagues with gastric cancer (OR=1.30, 95% CI: 1.07 to 1.58), history of chronic gastric disease (OR=1.90, 95% CI: 1.57 to 2.30), perceived high cost (OR=1.28, 95% CI: 1.01 to 1.61) and physician recommendation (OR=1.71, 95% CI: 1.36 to 2.16). On the other hand, factors negatively associated with screening attendance included perceived barriers, namely screening is only necessary when symptoms present (OR=0.71, 95% CI: 0.58 to 0.87) and perceived appointment for gastroscopy screening is difficult and time-consuming (OR=0.75, 95% CI: 0.60 to 0.94). No significant association was found between knowledge level and participation in screening. CONCLUSION: This study highlights important individual-level factors and barriers to gastric cancer screening. Strategies targeting under-screened populations and eliminating patient-perceived barriers to gastric cancer screening are essential.

Modulation of plasmonic chiral shell growth on gold nanorods via nonchiral surfactants.

Recently, in combination with seed-mediated growth, thiolated chiral molecule-guided growth has shown great promise in obtaining chiral plasmonic nanostructures. Previously, with the assistance of chiral cysteines (Cys), we realized helical growth of plasmonic shells on gold nanorod (AuNR) seeds dispersed in cetyltrimethylammonium bromide (CTAB) solution. Herein, we further studied the roles of non-chiral cationic surfactants in tuning the helical growth. Both the counter anion and the hydrocarbon chain length of the surfactants were found to affect the formation of helical shells greatly. In particular, we exhibited surfactant-modulated conversion of the chiral shell deposition mode between layer growth and island growth. By optimizing growth conditions, an obvious plasmonic circular dichroism (PCD) response could be achieved for the island helical shell. Our findings demonstrated promising potential of nanochemical synthesis in fabricating chiral plasmonic nanostructures with small structural sizes.

Esophageal mycobiome landscape and interkingdom interactions in esophageal squamous cell carcinoma.

Background: The study purpose was to characterize the mycobiome and its associations with the expression of pathogenic genes in esophageal squamous cell carcinoma (ESCC). Methods: Patients with primary ESCC were recruited from two central hospitals. We performed internal transcribed spacer 1 (ITS1) ribosomal DNA sequencing analysis. We compared differential fungi and explored the ecology of fungi and the interaction of bacteria and fungi. Results: The mycobiota diversity was significantly different between tumors and tumor-adjacent samples. We further analysed the differences between the two groups, at the species level, confirming that Rhodotorula toruloides, Malassezia dermatis, Hanseniaspora lachancei, and Spegazzinia tessarthra were excessively colonized in the tumor samples, whereas Preussia persica, Fusarium solani, Nigrospora oryzae, Acremonium furcatum, Golovinomyces artemisiae, and Tausonia pullulans were significantly more abundant in tumor-adjacent samples. The fungal co-occurrence network in tumor-adjacent samples was larger and denser than that in tumors. Similarly, the more complex bacterial-fungal interactions in tumor-adjacent samples were also detected. The expression of mechanistic target of rapamycin kinase was positively correlated with the abundance of N. oryzae and T. pullulans in tumor-adjacent samples. In tumors, the expression of MET proto-oncogene, receptor tyrosine kinase (MET) had a negative correlation and a positive correlation with the abundance of R. toruloides and S. tessarthra, respectively. Conclusion: This study revealed the landscape of the esophageal mycobiome characterized by an altered fungal composition and bacterial and fungal ecology in ESCC.

Spatial patterns and the associated factors for breast cancer hospitalization in the rural population of Fujian Province, China.

BACKGROUND: Despite the known increasing incidence of breast cancer in China, evidence on the spatial pattern of hospitalization for breast cancer is scarce. This study aimed to describe the disparity of breast cancer hospitalization in the rural population of Southeast China and to explore the impacts of socioeconomic factors and heavy metal pollution in soil. METHODS: This study was conducted using the New Rural Cooperative Medical Scheme (NRCMS) claims data covering 20.9 million rural residents from 73 counties in Southeast China during 2015-2016. The associations between breast cancer hospitalization and socioeconomic factors and soil heavy metal pollutants were evaluated with quasi-Poisson regression models and geographically weighted Poisson regressions (GWPR). RESULTS: The annual hospitalization rate for breast cancer was 101.40/100,000 in the studied area and the rate varied across different counties. Overall, hospitalization for breast cancer was associated with road density (ß = 0.43, P = 0.02), urbanization (ß = 0.02, P = 0.002) and soil cadmium (Cd) pollution (ß = 0.01, P = 0.02). In the GWPR model, a stronger spatial association of Cd, road density and breast cancer hospitalization was found in the northeast regions of the study area while breast cancer hospitalization was mainly related to urbanization in the western regions. CONCLUSIONS: Soil Cd pollution, road density, and urbanization were associated with breast cancer hospitalization in different regions. Findings in this study might provide valuable information for healthcare policies and intervention strategies for breast cancer.

The protective effect of H151, a novel STING inhibitor, in renal ischemia-reperfusion-induced acute kidney injury.

Renal ischemia-reperfusion (RIR)-induced acute kidney injury (AKI) is a common renal functional disorder with high morbidity and mortality. Stimulator of interferon (IFN) genes (STING) is the cytosolic DNA-activated signaling pathway that mediates inflammation and injury. Our recent study showed that extracellular cold-inducible RNA-binding protein (eCIRP), a newly identified damage-associated molecular pattern, activates STING and exacerbates hemorrhagic shock. H151 is a small molecule that selectively binds to STING and inhibits STING-mediated activity. We hypothesized that H151 attenuates eCIRP-induced STING activation in vitro and inhibits RIR-induced AKI in vivo. In vitro, renal tubular epithelial cells incubated with eCIRP showed increased levels of IFN-ß, STING pathway downstream cytokine, IL-6, tumor necrosis factor-α, and neutrophil gelatinase-associated lipocalin, whereas coincubation with eCIRP and H151 diminished those increases in a dose-dependent manner. In vivo, 24 h after bilateral renal ischemia-reperfusion, glomerular filtration rate was decreased in RIR-vehicle-treated mice, whereas glomerular filtration rate was unchanged in RIR-H151-treated mice. In contrast to sham, serum blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin were increased in RIR-vehicle, but in RIR-H151, these levels were significantly decreased from RIR-vehicle. In contrast to sham, kidney IFN-ß mRNA, histological injury score, and TUNEL staining were also increased in RIR-vehicle, but in RIR-H151, these levels were significantly decreased from RIR-vehicle. Importantly, in contrast to sham, in a 10-day survival study, survival decreased to 25% in RIR-vehicle, but RIR-H151 had a survival of 63%. In conclusion, H151 inhibits eCIRP-induced STING activation in renal tubular epithelial cells. Therefore, STING inhibition by H151 can be a promising therapeutic intervention for RIR-induced AKI.NEW & NOTEWORTHY Renal ischemia-reperfusion (RIR)-induced acute kidney injury (AKI) is a common renal functional disorder with a high morbidity and mortality rate. Stimulator of interferon genes (STING) is the cytosolic DNA-activated signaling pathway responsible for mediating inflammation and injury. Extracellular cold-inducible RNA-binding protein (eCIRP) activates STING and exacerbates hemorrhagic shock. H151, a novel STING inhibitor, attenuated eCIRP-induced STING activation in vitro and inhibited RIR-induced AKI. H151 shows promise as a therapeutic intervention for RIR-induced AKI.

Circulating Sex Hormone Levels and Risk of Gastrointestinal Cancer: Systematic Review and Meta-Analysis of Prospective Studies.

BACKGROUND: Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. METHODS: We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models. RESULTS: Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case-control, and three case-cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06-1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10-1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40-3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48-2.96), particularly in men (OR = 2.63; 95% CI, 1.65-4.18), Asian populations (OR = 3.27; 95% CI, 1.57-6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43-10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80-0.98 and OR = 0.88; 95% CI, 0.80-0.97, respectively) but not in women. CONCLUSIONS: Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer. IMPACT: Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.

Effects of preoperative albumin-to-globulin ratio on overall survival and quality of life in esophageal cell squamous carcinoma patients: a prospective cohort study.

OBJECTIVE: This study aimed to investigate the effect of preoperative albumin-to-globulin ratio (AGR) on overall survival (OS) and health-related quality of life in patients with esophageal cell squamous carcinoma (ESCC). METHODS: Serum albumin and globulin were measured within one week before surgery. Multiple follow-ups were conducted among patients with ESCC in the study in order to assess their life quality. The method used in the study was a telephone interview. Quality of life was measured using the EORTC Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30, version 3.0) and Esophageal Cancer Module (EORTC QLQ- OES18). RESULTS: A total of 571 ESCC patients were included in the study. The results illustrated that 5-year OS of high AGR group (74.3%) was better than the low one (62.3%) (P = 0.0068). Univariate and multivariate Cox regression analysis found that preoperative AGR (HR = 0.642, 95%CI: 0.444-0.927) are prognostic factor for patients with ESCC after surgery. In terms of quality of life, found that low AGR associated with increased postoperative time to deterioration (TTD) events in ESCC patients, and compared to low AGR, high AGR could delay the deterioration of emotional functioning(P = 0.001), dysphagia(P = 0.033), trouble with taste(P = 0.043) and speech problems(P = 0.043). After using the multivariate Cox regression analysis showed that high AGR could improve patients' emotional function (HR = 0.657, 95% CI: 0.507-0.852) and trouble with taste (HR = 0.706, 95% CI: 0.514-0.971). CONCLUSIONS: Preoperative AGR in patients with ESCC after esophagectomy was positively correlated with overall survival rate and quality of life after operation.

3D-bioprinted double-crosslinked angiogenic alginate/chondroitin sulfate patch for diabetic wound healing.

Improving chronic wound healing remains a challenge in the clinical practice. In this study, we developed double-crosslinked angiogenic 3D-bioprinted patches for diabetic wound healing by the photocovalent crosslinking of vascular endothelial growth factor (VEGF) using ultraviolet (UV) irradiation. 3D printing technology can precisely customize the structure and composition of patches to meet different clinical requirements. The biological polysaccharide alginate and chondroitin sulfate methacryloyl were used as biomaterials to construct the biological patch, which could be crosslinked using calcium ion crosslinking and photocrosslinking, thereby improving its mechanical properties. More importantly, acrylylated VEGF could be easily and rapidly photocrosslinked under UV irradiation, which simplified the step of chemically coupling growth factors and prolonged VEGF release time. These characteristics suggest that 3D-bioprinted double-crosslinked angiogenic patches are ideal candidates for diabetic wound healing and other tissue engineering applications.

The Landscape of Lipid Metabolism in Lung Cancer: The Role of Structural Profiling.

The aim of this study was to explore the relationship between lipids with different structural features and lung cancer (LC) risk and identify prospective biomarkers of LC. Univariate and multivariate analysis methods were used to screen for differential lipids, and two machine learning methods were used to define combined lipid biomarkers. A lipid score (LS) based on lipid biomarkers was calculated, and a mediation analysis was performed. A total of 605 lipid species spanning 20 individual lipid classes were identified in the plasma lipidome. Higher carbon atoms with dihydroceramide (DCER), phosphatidylethanolamine (PE), and phosphoinositols (PI) presented a significant negative correlation with LC. Point estimates revealed the inverse associated with LC for the n-3 PUFA score. Ten lipids were identified as markers with an area under the curve (AUC) value of 0.947 (95%, CI: 0.879-0.989). In this study, we summarized the potential relationship between lipid molecules with different structural features and LC risk, identified a panel of LC biomarkers, and demonstrated that the n-3 PUFA of the acyl chain of lipids was a protective factor for LC.

Short-term and long-term effects of Sanming healthcare system reform on drug-related expenditures for rural patients with cancer in public hospitals: an interrupted time series analysis using segmented regression model in China.

OBJECTIVES: To assess the effects of 'Sanming model' on drug-related expenditures. DESIGN: Interrupted time series analysis with two time points was conducted to analyse the effects of 'Sanming model' using segmented regression model. SETTING: Two hundred and eighty public hospitals in Fujian province in China. PARTICIPANTS: A total of 777 171 inpatients and 792 743 outpatients with cancer who participated in New Rural Cooperative Medical Scheme (NRCMS) were included. INTERVENTIONS: 'Sanming model' was issued by Sanming government in February 2013 and spread to other cities in Fujian province in January 2015. PRIMARY OUTCOME MEASURES: Four drug-related expenditure variables. RESULTS: Among inpatients, total drug expenditures and drug expenditures covered by NRCMS dropped instantly after the reform in all hospitals. Although there was insignificant change during the short-term reform period, the total drug expenditures and drug expenditures covered by NRCMS decreased at the rate of ¥20.3 (p=0.0099) and ¥18.8 (p=0.0341) per capita month-to-month during the long-term reform period in Sanming hospitals, respectively. Among outpatients, total drug expenditures and drug expenditures covered by NRCMS decreased at the rate of ¥20.8 (p=0.0335) and ¥18.4 (p=0.0242) per capita month-to-month during the short-term reform period in Sanming hospitals, respectively. However, the downward trend did not continue into the long term. The significant decreases in trend of drug expenditures uncovered by NRCMS were only observed after the reform in provincial hospitals. The ratio of drug expenditures to inpatient (outpatient) expenditures decreased after the reform in all hospitals. CONCLUSIONS: 'Sanming model' had long-term effect in reducing total drug expenditures, drug ratio and drug expenditures covered by NRCMS for rural inpatients with cancer and only short-term positive effect for outpatients. However, there was limited effect of 'Sanming model' on drug expenditures uncovered by NRCMS. 'Sanming model' still needs to accumulate experiences and improves the reform measures dynamically.

Association between physical activity and health-related quality of life: time to deterioration model analysis in lung adenocarcinoma.

BACKGROUND AND PURPOSE : Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD). METHODS: We conducted a hospital-based prospective study. The International Physical Activity Questionnaire long-form (IPAQ-L) was used to investigate the pre-treatment physical activity levels, and the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) were used to assess HRQoL at baseline and during follow-up. The QoLR package was used to calculate the HRQoL scores and determine TTD events (minimal clinically important difference=5 points). The effect of physical activity on the HRQoL was assessed using Cox regression analysis. RESULTS: For EORTC QLQ-C30, TTD events of physical functioning (PF) and dyspnea (DY) in functional scales and symptom scales were the most common during follow-up. Pre-treatment physical activity was found to significantly delay TTD of insomnia (HR=0.635, 95%CI: 0.437-0.922, P=0.017) and diarrhea (HR=0.475, 95%CI: 0.291-0.774, P=0.003). For EORTC QLQ-LC13 scales, deterioration of dyspnea (LC-DY) was the most common event. Physical activity was found to delay the TTD of dyspnea (HR=0.654, 95%CI: 0.474-0.903, P=0.010), sore mouth (HR=0.457, 95%CI: 0.244-0.856, P=0.015), and dysphagia (HR=0.315, 95%CI: 0.172-0.580, P<0.001). CONCLUSIONS: Pre-treatment physical activity of LUAD patients may delay the TTD of multiple HRQoL indicators in EORTC QLQ-C30 and EORTC QLQ-LC13. IMPLICATION FOR CANCER SURVIVORS: Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors (someone who is living with or beyond cancer), that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD).

Dietary Inflammatory Nutrients and Esophageal Squamous Cell Carcinoma Risk: A Case-Control Study.

We conducted a case-control study (532 cases and 532 control) in Chinese adults to investigate the independent and interactive effects of dietary nutrients (pro- or anti-inflammation) on Esophageal Squamous Cell Carcinoma (ESCC) risk. Dietary data were collected using a food questionnaire survey that included 171 items. Two algorithms, the Least Absolute Shrinkage and Selector Operation (LASSO) and Bayesian Kernel Machine Regression (BKMR) were employed to select indicators and evaluate the interactive effect of nutrients' mixture on ESCC risk. Thirteen nutrients were selected, including three pro-inflammatory nutrients (protein, fat and carbohydrate) and ten anti-inflammatory nutrients (fiber, Vitamin A, riboflavin, niacin, Vitamin C, Fe, Se, MUFA, n-3 PUFA and n-6 PUFA). Single-exposure effects of fat, carbohydrate and fiber significantly contributed to ESCC risk. The pro-inflammatory nutrients' submodel discovered that the combined effect was statistically associated with increased ESCC risk. In addition, a higher fat level was significantly associated with ESCC risk. On the contrary, for fiber and riboflavin, the anti-inflammatory nutrients' submodel delineated a significant negative effect on the risk of ESCC. Our result implies that dietary nutrients and their inflammatory traits significantly impacted ESCC occurrence. Additional studies are warranted to verify our findings.

Development and Validation of a Prognostic Model for Esophageal Adenocarcinoma Based on Necroptosis-Related Genes.

Necroptosis is a newly developed cell death pathway that differs from necrosis and apoptosis; however, the potential mechanism of necroptosis-related genes in EAC and whether they are associated with the prognosis of EAC patients remain unclear. We obtained 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and performed differential expression analysis of the NRGs in 9 normal samples and 78 EAC tumor samples derived from The Cancer Genome Atlas (TCGA). Finally, we screened 38 differentially expressed NRGs (DE-NRGs). The results of the GO and KEGG analyses indicated that the DE-NRGs were mainly enriched in the functions and pathways associated with necroptosis. Protein interaction network (PPI) analysis revealed that TNF, CASP1, and IL-1B were the core genes of the network. A risk score model based on four DE-NRGs was constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression, and the results showed that the higher the risk score, the worse the survival. The model achieved more efficient diagnosis compared with the clinicopathological variables, with an area under the receiver operating characteristic (ROC) curve of 0.885. The prognostic value of this model was further validated using Gene Expression Omnibus (GEO) datasets. Gene set enrichment analyses (GSEA) demonstrated that several metabolism-related pathways were activated in the high-risk population. Single-sample GSEA (ssGSEA) provided further confirmation that this prognostic model was remarkably associated with the immune status of EAC patients. Finally, the nomogram map exhibited a certain prognostic prediction efficiency, with a C-index of 0.792 and good consistency. Thus, the prognostic model based on four NRGs could better predict the prognosis of EAC and help to elucidate the mechanism of necroptosis-related genes in EAC, which can provide guidance for the target prediction and clinical treatment of EAC patients.